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ÓÕÍÏÕÊËÅÚÍÅÓ 643 

ÁÍÁÓÊÏÐÇÓÇ 

ÁÑ×ÅÉÁ ÅËËÇÍÉÊÇÓ ÉÁÔÑÉÊÇÓ 2003, 20(6):643–653 

REVIEW 

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ÓõíïõêëåÀíåò 

NÝåò ðñïïðôéêÝò ãéá ôá íïóÞìáôá 

ôïõ íåõñéêïý óõóôÞìáôïò 

ÅðéóôçµïíéêÝò µåëÝôåò Ý÷ïõí õðïäåßîåé ôçí ýðáñîç µéáò ïì Üäáò ðñùôåúíþí 

ðïõ ïíïìÜæïíôáé óõíïõêëåÀíåò êáé åíôïðßæïíôáé êõñßù ò óôï êåíôñéêü 

êáé ðåñéöåñéêü íåõñéêü óýóôçµá. Ðñüêåéôáé ãéá ìéêñÝò, õ äáôïäéáëõôÝò 

ðñùôåÀíåò, ðïõ ÷áñáêôçñßæïíôáé áðü ôçí ýðáñîç üîéíùí áìéíïîÝùí 

óôï êáñâïîõëéêü Üêñï ôçò ðñùôåÀíçò, êáèþò êáé åðáíáëáìâáí üìåíùí, 

åêöõëéóôéêþí áëëçëïõ÷éþí áìéíïîÝùí, ðïõ óõíáíôþíôáé êáé óôéò áðïëéðïðñùôåÀíåò. 

¼óïí áöïñÜ óôçí ðáèïëïãßá, ïé óõíïõêëåÀíåò ó õììåôÝ- 

÷ïõí óå ìéá óåéñÜ ðïëýðëïêùí êáé óïâáñþí íåõñïðáèåéþí êáé Üëëùí 

íïóçìÜôùí. Ç ïìÜäá ôùí óõíïõêëåúíïðáèåéþí óõíéóôÜ ìéá ïìÜäá íåõñïåêöõëéóôéêþí 

íïóçìÜôùí, ðïõ êïéíü ðáèïëïãéêü ôïõò åýñç ìá áðïôåëïýí 

ïé åíáðïèÝóåéò ìç Salvens á-óõíïõêëåÀíçò åðéëåêôéêÜ óå åõð áèåßò 

ïìÜäåò íåõñþíùí êáé ãëïéáêþí êõôôÜñùí. Óå áõôÞ ôçí ïìÜäá á íÞêïõí 

ç íüóïò Alzheimer, ç íüóïò Parkinson, ç óêëÞñõíóç êáôÜ ðëÜêáò, ç íüóïò 

ìå óùìáôßäéá Lewy (Lewy body dementia), ç íüóïò ôïõ Pick, ç áìõïôñïöéêÞ 

ðëåõñéêÞ óêëÞñõíóç, ï íåõñïåêöõëéóìüò ìå óõóóþñå õóç óéäÞñïõ 

(ôýðïò 1) êáé ç ôñáõìáôéêÞ åãêåöáëéêÞ âëÜâç. Ç â-óõíïõê ëåÀíç 

öáßíåôáé íá óõììåôÝ÷åé åðßóçò óå íåõñïåêöõëéóôéêÝò ðáèÞ óåéò áëëÜ ìå 

ëéãüôåñï åíåñãü ñüëï, åíþ ç ã-óõíïõêëåÀíç áðáíôÜôáé êáé óå íåïðëáóìáôéêÝò 

ðáèÞóåéò, êõñßùò óôï ìáóôü êáé ôéò ùïèÞêåò Ç ã-óõí ïõêëåÀíç 

åìðëÝêåôáé óå êáñêéíéêÝò êáôáóôÜóåéò, êõñßùò ôïõ ìáóôïý ê áé ôùí ùïèçêþí, 

åíþ êáé ç â-óõíïõêëåÀíç öáßíåôáé íá óõììåôÝ÷åé óå íå õñïåêöõëéóôéêÜ 

íïóÞìáôá. Ç áíáóêüðçóç áõôÞ êáôáãñÜöåé ôéò ãíþóåé ò ó÷åôéêÜ 

ìå ôï öõóéïëïãéêü ñüëï ôùí óõíïõêëåúíþí, ï ïðïßïò ðáñáìÝí åé áäéåõêñßíéóôïò, 

êáé ôç óõììåôï÷Þ ôïõò óôçí ðáèïãÝíåóç ôçò íüóï õ Parkinson 

êáé Üëëùí íïóçìÜôùí. 

1. ÅÉÓÁÃÙÃÇ 

Ïé íåõñïåêöõëéóôéêÝò ðáèÞóåéò ðñïóâÜëëïõí ðëÝïí 

Ýíá óçìáíôéêü ðïóïóôü ôïõ ðëçèõóìïý ôùí óýã÷ñïíùí 

äõôéêþí êïéíùíéþí. Tá ôåëåõôáßá ÷ñüíéá êáôáâÜëëåôáé 

ìéá óõóôçìáôéêÞ ðñïóðÜèåéá áðïóáöÞíéóçò ôùí ðáèïãåíåôéêþí 

ðáñáãüíôùí áõôþí ôùí íïóçìÜôùí, ôá ïðïßá 

ðéóôåýåôáé üôé, áíåîÜñôçôá áðü ôç óõìðôùìáôïëïãßá, óå 

Ýíá ìåãÜëï âáèìü áêïëïõèïýí êïéíïýò ìç÷áíéóìïýò 

ðáèïãÝíåóçò. Óôçí ðñïóðÜèåéá áõôÞ óõíôåëåß ç åöáñìïãÞ 

ôçò ìïñéáêÞò âéïëïãßáò êáé ç áðüêôçóç åõñçìÜôùí 

ó÷åôéêÜ ìå ôç ãåíåôéêÞ êáé âéï÷çìéêÞ ôïõò âÜóç. Ç 

áíáóêüðçóç áõôÞ áöïñÜ êõñßùò óôá óôïé÷åßá ãéá ôï 

öõóéïëïãéêü êáé ðáèïëïãéêü ñüëï ôùí óõíïõêëåúíþí, 

ìéáò íåïåìöáíéæüìåíçò ïìÜäáò ðñùôåúíþí óå íåõñïåêöõëéóôéêÝò 

ðáèÞóåéò. Ç ïìÜäá áðïôåëåßôáé áðü 3 

ARCHIVES OF HELLENIC MEDICINE 2003, 20(6):643–653 

Ê. Ðáðá÷ñüíç, 1 

Á. Ðáðáäçìçôñßïõ, 2 

Á. Êáëïöïýôçò1 ..................................................... 

1 ÅñãáóôÞñéï ÂéïëïãéêÞò ×çìåßáò, ÉáôñéêÞ 

Ó÷ïëÞ Áèçíþí, ÐáíåðéóôÞìéï Áèçíþí, 

ÁèÞíá 

2 ÍåõñïëïãéêÞ ÊëéíéêÞ, ÉáôñéêÞ Ó÷ïëÞ 

ËÜñéóáò, ÐáíåðéóôÞìéï Èåóóáëßáò, 

ËÜñéóá 

Synucleins: Íew prospects in the 

diseases of the nervous system 

Abstract at the end of the article 

ËÝîåéò åõñåôçñßïõ 

ÐñùôåÀíåò 14-3-3, PD, MS, AD 

ÓõíïõêëåÀíç á, â, ã 

ôºªÖóΠƒ í£ 20.12.2002 

äÜí¿σƒ í£ 25.2.2003 

ìÝëç-ðñùôåÀíåò, ôéò á, â êáé ã êáé ìéá ôÝôáñôç, ôç óõíïñÝôç, 

ãéá ôçí ïðïßá üìùò õðÜñ÷åé áìöéâïëßá áí ðñüêåéôáé 

ãéá îå÷ùñéóôü ìÝëïò Þ õðï-ìÝëïò ôçò ã-óõíïõêëåÀíçò, 

ëüãù ôïõ ìåãÜëïõ âáèìïý ãåíåôéêÞò ïìïéüôçôÜò 

ôïõò. 1 

2. ÂÉÏ×ÇÌÉÊÁ ×ÁÑÁÊÔÇÑÉÓÔÉÊÁ ÓÕÍÏÕÊËÅÚÍÙÍ 

Ïé óõíïõêëåÀíåò åßíáé ìéêñÝò (110–140 áìéíïîÝá), 

õäáôïäéáëõôÝò ðñùôåÀíåò. ×áñáêôçñßæïíôáé áðü ôçí ðáñïõóßá 

üîéíùí áìéíïîÝùí óôï êáñâïîõëéêü Üêñï ôçò ðñùôåÀíçò 

êáé ôçí ðáñïõóßá åðáíáëáìâáíüìåíùí, åêöõëéóôéêþí 

áëëçëïõ÷éþí áìéíïîÝùí (ìå ôçí áêïëïõèßá 

KTKEGVLYVGS) óôï áìéíïôåëéêü Üêñï, 2 ðåñéïäéêüôçôá 

áìéíïîÝùí ðïõ óõíáíôÜôáé êõñßùò óå ìéá Üëëç, êáëþò 

÷áñáêôçñéóìÝíç ïìÜäá ðñùôåúíþí, ôéò áðïëéðïðñùôåÀíåò.

644 Ê. ÐÁÐÁ×ÑÏÍÇ êáé óõí 

Ôï üíïìá óõíïõêëåÀíåò (synucleins) äüèçêå ãéá ðñþôç 

öïñÜ óå ìéá ðñùôåÀíç ðïõ áðïìïíþèçêå áðü ôïí ïñãáíéóìü 

Torpedo californica, êáèþò åíôïðßóôçêå óôçí (ðñï)óõíáðôéêÞ 

ðåñéï÷Þ êáé óôçí ðõñçíéêÞ (nuclear) ìåìâñÜíç 

ôïõ íåõñéêïý êõôôÜñïõ. 3 ÁõôÞ ç ðñùôåÀíç áðïôåëåß 

ôï ðñþôï ìÝëïò ôçò ïìÜäáò êáé óçìåßï áíáöïñÜò ãéá 

ôá õðüëïéðá ìÝëç. Óôïí Üíèñùðï Ý÷ïõí åíôïðéóôåß ç á, 

â êáé ã-óõíïõêëåÀíç, ïé ïðïßåò Ý÷ïõí 75–80% ïìïéüôçôá 

áëëçëïõ÷ßáò ìå ôçí ðáñáðÜíù óõíïõêëåÀíç êáé åßíáé 

ðñïúüíôá ôñéþí äéáöïñåôéêþí ãïíéäßùí (4q21, 4 

5q35, 5 10q23.2–q23.3, 6 áíôßóôïé÷á). Ïé óõíïõêëåÀíåò 

á êáé â óôïí Üíèñùðï áðïìïíþèçêáí áðü ôïí åãêÝöáëï 

ùò áíôéãüíá ôïõ áíôéóþìáôïò åíáíôßïí ôçò ðñùôåÀíçò 

Ô, 7,8 ç ïðïßá óôïí åãêÝöáëï åêöñÜæåôáé óôá íåõñéêÜ 

êýôôáñá, ôá áóôñïêýôôáñá êáé ôá ïëéãïäåíäñïêýôôáñá 

êáé âáóéêüò ñüëïò ôçò åßíáé ç ñýèìéóç ôçò óôáèåñüôçôáò 

êáé ôïõ ðñïóáíáôïëéóìïý ôùí ìéêñïóùëçíßóêùí óôïí 

êõôôáñéêü óêåëåôü. ÅíáðïèÝóåéò ôçò ðñùôåÀíçò Ô åíôïðßæïíôáé 

óôïí åãêÝöáëï áóèåíþí ìå ôç íüóï Alzheimer 

êáé ôï ðëÞèïò ôùí åíáðïèÝóåùí áõôþí åßíáé áíÜëïãï 

ìå ôçí åðéèåôéêüôçôá ôïõ íïóÞìáôïò êáé ôçí Ýêôáóç ôçò 

êëéíéêÞò óõìðôùìáôïëïãßáò. Ç ã-óõíïõêëåÀíç áðïìïíþèçêå 

óôïí Üíèñùðï ôáõôü÷ñïíá áðü êáñêéíéêÜ êýôôáñá 

ôïõ ìáóôïý êáé áðü íåõñéêü éóôü êáé åêöñÜæåôáé óôï 

êåíôñéêü êáé ðåñéöåñéêü íåõñéêü óýóôçìá êáé óå íåïðëáóìáôéêÜ 

êýôôáñá ôïõ ìáóôïý êáé ôùí ùïèçêþí. 

Ç á-óõíïõêëåÀíç áðïôåëåß ðÜíù áðü ôï 1% ôïõ óõíïëéêïý 

ðëÞèïõò ðñùôåúíþí óôá õäáôïäéáëõôÜ åãêåöáëéêÜ 

êëÜóìáôá. ÊÜôù áðü öõóéïëïãéêÝò óõíèÞêåò äåí 

êáôáëáìâÜíåé óõãêåêñéìÝíç óôåñåïäïìÞ (natively unfolded) 

êáé ðáñïõóéÜæåé ÷áìçëÞ õäñïöïâéêüôçôá êáé ìåãÜëï 

öïñôßï. 9 Ç â-óõíïõêëåÀíç Ý÷åé 78% ïìïëïãßá êáé 

ïìüëïãï êáñâïîõëéêü Üêñï ìå ôçí á-óõíïõêëåÀíç, áëëÜ 

õðïëåßðåôáé 11 áìéíïîÝùí óôç ìÝóç ðåñéï÷Þ êáé áõôü 

ôçò äßíåé ôçí ðåñéóóüôåñï ïñãáíùìÝíç äïìÞ ôïõ ôõ- 

÷áßïõ Ýëéêá. 9 Ç ã-óõíïõêëåÀíç Ý÷åé 60% ãåíåôéêÞ ïìïëïãßá 

ìå ôçí á-óõíïõêëåÀíç, áëëÜ õðïëåßðåôáé ôïõ üîéíïõ, 

ôõñïóéíéêïý, êáñâïîõëéêïý Üêñïõ, ðïõ Ý÷ïõí êáé 

ïé äýï Üëëåò ðñùôåÀíåò. Ùóôüóï, Ý÷åé ðåñéóóüôåñï ïñãáíùìÝíç 

äïìÞ. 10–12 

Ïé ðåñéï÷Ýò êáé ï ÷ñüíïò Ýêöñáóçò ôùí óõíïõêëåúíþí 

ìåëåôÞèçêå óôïí Üíèñùðï óôç ìÝëáéíá ïõóßá ôïõ 

åãêåöÜëïõ. Ç á êáé ç â-óõíïõêëåÀíç åêöñÜæïíôáé áñ- 

÷éêÜ óôï êõôôáñüðëáóìá ôïõ íåõñéêïý êõôôÜñïõ (15ç 

êáé 17ç åâäïìÜäá åìâñõúêÞò çëéêßáò, áíôßóôïé÷á) 13 êáé 

óôáäéáêÜ ìåôáêéíïýíôáé ðñïò ôçí ðñïóõíáðôéêÞ ðåñéï- 

÷Þ (18ç êáé 33ç åâäïìÜäá åìâñõúêÞò çëéêßáò, áíôßóôïé- 

÷á), üðïõ êáé åíôïðßæïíôáé óå üëá ôá ìåôÝðåéôá óôÜäéá 

áíÜðôõîçò. ºäéï ÷ùñï-÷ñïíéêü ìïôßâï Ýêöñáóçò ðáñïõ- 

óéÜæïõí êáé äýï Üëëåò ãíùóôÝò óõíáðôéêÝò ðñùôåÀíåò, 

ç óõíáðôïöõóßíç êáé ç óõíáðôïâñåâßíç (synaptobrevin), 

ôùí ïðïßùí ï ñüëïò óôç öõóéïëïãßá ôïõ íåõñéêïý êõôôÜñïõ 

êáé åéäéêÜ óôçí áíÜðôõîç ôùí óõíÜøåùí åßíáé 

äåäïìÝíïò. 14,15 Áõôü áðïôåëåß åðéðëÝïí óôïé÷åßï óå ìéá 

áðü ôéò åðéêñáôïýóåò áðüøåéò ó÷åôéêÜ ìå ôï ñüëï ôùí 

óõíïõêëåúíþí, ðïõ áöïñÜ óôç óõììåôï÷Þ ôïõò óôçí 

áíÜðôõîç êáé åîÝëéîç ôùí óõíÜøåùí êáé ôçò ìÝëáéíáò 

ïõóßáò. 16 Ç ã-óõíïõêëåÀíç óå êõôôáñéêü åðßðåäï åßíáé 

ðåñéóóüôåñï äéáóðáñìÝíç óôï êõôôáñüðëáóìá êáé âñßóêåôáé 

óôá êõôôáñéêÜ óþìáôá êáé óôïõò íåõñÜîïíåò. 17 

3. ÖÕÓÉÏËÏÃÉÊÏÓ ÑÏËÏÓ ÔÙÍ ÓÕÍÏÕÊËÅÚÍÙÍ 

Ï áêñéâÞò ñüëïò ðïõ äéáäñáìáôßæïõí ïé óõíïõêëåÀíåò 

óôï êýôôáñï êÜôù áðü öõóéïëïãéêÝò óõíèÞêåò ðáñáìÝíåé 

áäéåõêñßíéóôïò. Ôá ôåëåõôáßá ÷ñüíéá, ìå ôçí 

áíáêÜëõøç ðùò ïé óõãêåêñéìÝíåò ðñùôåÀíåò åìðëÝêïíôáé 

óôçí ðáèïãÝíåéá ìéáò óåéñÜò íïóçìÜôùí (ðßíáêåò 

1, 2, 3), êáôáâÜëëåôáé óõíôïíéóìÝíç ðñïóðÜèåéá äéåñåýíçóçò 

ôçò ëåéôïõñãßáò ôïõò. Ôá åõñÞìáôá åßíáé ðïëëÜ, 

áëëÜ Ýíá ïëïêëçñùìÝíï ìïíôÝëï ëåéôïõñãßáò êáé 

ìç÷áíéóìïý äñÜóçò äåí Ý÷åé áêüìá åðéôåõ÷èåß, êáèþò 

ôï áíôéêåßìåíï åîåôÜæåôáé êÜôù áðü äéáöïñåôéêÝò ðåéñáìáôéêÝò 

óõíèÞêåò êáé áõôü öáßíåôáé íá åðçñåÜæåé ôçí 

ôåëéêÞ åñìçíåßá ôïõ ñüëïõ ôïõ. 

Ìéá áðü ôéò ðëÝïí åíäéáöÝñïõóåò áíáêáëýøåéò ó÷åôßæåôáé 

ìå ôç óõììåôï÷Þ ôùí óõíïõêëåúíþí óôïõò ìç÷áíéóìïýò 

êõôôáñéêÞò åðéêïéíùíßáò. ÅõñÞìáôá äåß÷íïõí 

üôé ïé óõíïõêëåÀíåò ìðïñåß íá äéáäñáìáôßæïõí ñüëï 

óôçí áíáäéïñãÜíùóç ôïõ êõôôáñéêïý óêåëåôïý êáé ôçí 

åíäïêõôôÜñùóç, êáèþò êáé óôçí Ýêêñéóç êÜðïéùí íåõñïäéáâéâáóôþí 

ìÝóù ôçò ñýèìéóçò ôçò ëåéôïõñãßáò ôùí 

öùóöïëéðáóþí. ÓõãêåêñéìÝíá, ïé Colley et al 42 åíôüðéóáí 

üôé ç á êáé ç â-óõíïõêëåÀíç áðåíåñãïðïéïýí ôç 

öùóöïëéðÜóç D 2 (PLD 2) ìÝóù ôùí óõæåõãìÝíùí ìå ôéò 

g ðñùôåÀíåò êéíáóþí (g protein coupled kinases, GRKs) 

êáé ñõèìßæïõí êáô’ áõôüí ôïí ôñüðï ôçí Ýêêñéóç ôçò 

íôïðáìßíçò. 42–44 ÅðéðëÝïí, ïé Davidson et al 45 Ýäåéîáí 

üôé ïé óõíïõêëåÀíåò áëëçëåðéäñïýí ìå ôá êõóôßäéá ðïõ 

ðåñéÝ÷ïõí üîéíá öùóöïëéðßäéá êáé ïé Perrin et al 46 åíôüðéóáí 

üôé ôï ìÝñïò ôçò ðñùôåÀíçò ðïõ åìðëÝêåôáé óå 

áõôÞ ôçí áëëçëåðßäñáóç êáôáëáìâÜíåé ôá äýï ôñßôá 

ôïõ ìïñßïõ. ÓõìðëçñùìáôéêÜ, ïé Eliezer et al 47 Ýäåéîáí 

üôé ç óõíïõêëåÀíç, êáôÜ ôçí åðáöÞ ìå ôá öùóöïëéðßäéá, 

êáôáëáìâÜíåé äåõôåñïãåíÞ ïñãÜíùóç üìïéá ìå áõôÞ 

ôçò ôÜîçò Á 2 ôùí áðïëéðïðñùôåúíþí. Ç Ýêêñéóç, ç óõãêÝíôñùóç 

êáé ï ìåôáâïëéóìüò ôçò íôïðáìßíçò Ý÷ïõí 

éäéáßôåñï ñüëï óôçí åêäÞëùóç êáé åîÝëéîç ôçò íüóïõ


Ðßíáêáò 1. ÍïóÞìáôá óôá ïðïßá åìðëÝêåôáé ç á-óõíïõêëåÀíç. 

ÍïóÞìáôá Ðáèïëïãßá ó÷åôéêÞ ìå ôçí á-óõíïõêëåÀíç ÁíáöïñÝò 

Íüóïò Álzheimer Ó÷çìáôéóìüò óùìáôéäßùí Lewy êáé íåõñïúíéáêþí ìáæþí Masliah et al, 2000 18 

Lippa et al, 1999 19 

Marui et al, 2000 20 

Matsubara et al, 2001 21 

ÁìõïôñïöéêÞ ðëåõñéêÞ óêëÞñõíóç Óõóóþñåõóç íåõñïãëïéáêþí êõôôÜñùí óôç óðïíäõëéêÞ óôÞëç Mezey et al, 1998 12 

¢íïéá ìå ó÷çìáôéóìü óùìáôéäßùí Lewy Óùìáôßäéá Lewy, ù÷ñÜ óùìáôßäéá, íåõñßôåò Lewy, äõóôñïöéêïß íåõñßôåò Spillantini et al, 1998 22 

Wakabayashi et al, 1999 23 

Óýíäñïìï Down Óùìáôßäéá Lewy Lippa et al, 1999 19 

Íüóïò Huntington ÅíäïðõñçíéêÝò åíáðïèÝóåéò Charles et al, 2000 24 

Ìõïóßôéäá ìå Ýãêëåéóôá óùìáôßäéá Êåíïôïðéþäç ìõúêÜ éíßäéá Askanas et al, 2000 25 

Óõããåíéêü ðñoúüí ôýðïõ Indiana Óõóóþñåõóç óùìáôéäßùí ðáñåìöåñþí ìå ôá óùìáôßäéá Lewy Hardy, 1998 26 

ÓêëÞñõíóç êáôÜ ðëÜêáò ÊõôôáñïðëáóìáôéêÝò åíáðïèÝóåéò óå ãëïéáêÜ êýôôáñá Spillantini et al, 1998 22 

Gai et al, 1998 27 


Íåõñïåêöõëéóìüò ìå óõóóþñåõóç Ó÷çìáôéóìüò óùìáôéäßùí Lewy êáé óöáéñïåéäþí óôá áîüíéá Arakawa et al, 1998 28 

óéäÞñïõ óôïí åãêÝöáëï, ôýðïò 1 Wakabayashi et al, 1999 23 

Galvin et al, 2000 29 

Saito et al, 2000 30 

Íüóïò Parkinson Spillantini et al, 1998 22 


Irizarry et al, 1998 31 

Braak et al, 1999 32 

Galvin et al, 2000 33 

Hurtig et al, 2000 34 

Braak et al, 2001 35 

Óýìðëåãìá ðáñêéíóïíéêÞò óõíäñïìÞò Ó÷çìáôéóìüò óùìáôéäßùí Lewy Yamazaki et al, 200036 êáé Üíïéáò ôïõ Guam 

Íüóïò Pick Ó÷çìáôéóìüò óùìáôéäßùí Pick óôïí éððüêáìðï Goedert, 19998 Galvin et al, 200029 ÁêÝñáéç áõôïíïìéêÞ áíåðÜñêåéá Ó÷çìáôéóìüò óùìáôéäßùí Lewy Kaufmann et al, 200137 ÔñáõìáôéêÞ åãêåöáëéêÞ âëÜâç ÖëåãìïíÞ ôùí áîüíùí Newell et al, 199938 Ðßíáêáò 2. ÍïóÞìáôá óôá ïðïßá åìðëÝêåôáé ç â-óõíïõêëåÀíç. 

ÍïóÞìáôá Ðáèïëïãßá ó÷åôéêÞ ìå ôç â-óõíïõêëåÀíç ÁíáöïñÝò 

¢íïéá ìå ó÷çìáôéóìü óùìáôéäßùí Lewy Ó÷çìáôéóìüò óôïí éððüêáìðï äõóôñïöéêþí íåõñéôþí Galvin et al, 2000 33 

Íüóïò Parkinson Ó÷çìáôéóìüò äõóôñïöéêþí íåõñéôþí Galvin et al, 2000 33 

Parkinson êáé ïé âéï÷çìéêÝò ïäïß ðïõ ôéò ñõèìßæïõí êáé 

áöïñïýí ôçí á-óõíïõêëåÀíç óõììåôÝ÷ïõí óôçí ðáèïãÝíåóç 

ôçò íüóïõ. 

Ïé óõíïõêëåÀíåò áëëçëåðéäñïýí åðßóçò ìå ðïëõáêüñåóôá 

ëéðßäéá (poly-unsaturated fatty acids, PUFA) êáé 

áõôÞ ç åðáöÞ ðñïêáëåß ôïí ôá÷ý ðïëõìåñéóìü ôùí óõíïõêëåúíþí, 

êáèþò êáé ìå ìÝëç ôçò ïìÜäáò ôùí ìéôïãïíéêþò 

åíåñãïðïéçìÝíùí ðñùôåúíéêþí êéíáóþí (mitogen 

activated protein kinase, MAPK), ôùí ïðïßùí ç ëåéôïõñãßá 

Ý÷åé óõíäåèåß ìå ìéá óåéñÜ åñåèéóìÜôùí ðïõ áöï- 

ñïýí óôçí áíÜðôõîç, ôïí ðïëëáðëáóéáóìü, ôç äéáöïñïðïßçóç 

êáé ôçí áðüðôùóç ôùí êõôôÜñùí. 48,49 

3.1. ÓõíïõêëåÀíåò êáé ïìÜäá ðñùôåúíþí 14-3-3 

Åðßóçò, ïé óõíïõêëåÀíåò Ý÷ïõí 40% ïìïéüôçôá áëëçëïõ÷ßáò 

óôï áìéíïôåëéêü Üêñï ìå ôéò ðñùôåÀíåò 14-3-3, 

ïé ïðïßåò åêöñÜæïíôáé åêôåíþò óôïí åãêÝöáëï êáé ìåôáöÝñïõí 

ðñùôåÀíåò, ìåôáîý ôùí ïðïßùí êáé êÜðïéåò 

ðïõ óõììåôÝ÷ïõí óôçí êõôôáñéêÞ åðéêïéíùíßá, üðùò ç 

öùóöïëéðÜóç C (phospholipase C, PK C) êáé ïé ðñùôåÀ-


Ðßíáêáò 3. ÍïóÞìáôá óôá ïðïßá åìðëÝêåôáé ç ã-óõíïõêëåÀíç. 

ÍïóÞìáôá Ðáèïëïãßá íüóïõ ðïõ ó÷åôßæåôáé ìå ôç ã-óõíïõêëåÀíç ÁíáöïñÝò 

Êáñêßíïò ìáóôïý ÕðåñÝêöñáóç ðñùôåÀíçò Ji et al, 1997 39 

íåò BAD, ERK êáé Raf-1, 50,51 êáé ñõèìßæïõí ôçí åîùêõôôÜñùóç, 

ôçí áðüðôùóç êáé ôç äéÜâáóç ôïõ êõôôáñéêïëý 

êýêëïõ. Ç á-óõíïõêëåÀíç áëëçëåðéäñÜ ìå ôéò ßäéåò ðñùôåÀíåò 

êáé ó÷çìáôßæåé óýìðëïêá ìå ìç ëåéôïõñãéêÜ/äýóìïñöá 

ðñùôåúíéêÜ ìüñéá, áìâëýíïíôáò ðéèáíÝò ôïîéêÝò 

ôïõò óõíÝðåéåò. 52,53 Ïé ðñùôåÀíåò 14-3-3 åëÝã÷ïõí åðßóçò 

ôç ëåéôïõñãßá ôïõ åíæýìïõ õäñïîõëÜóç ôçò ôõñïóßíçò 

ãéá ôç óýíèåóç ôçò íôïðáìßíçò. Ïé Perez et al 

(2002) 54 ðñüôåéíáí üôé ç á-óõíïõêëåÀíç êáé ìéá ðñùôåÀíç 

14-3-3 âñßóêïíôáé óå äõíáìéêÞ éóïññïðßá ãéá ôç 

ñýèìéóç ôçò ëåéôïõñãßáò ôïõ åíæýìïõ. ÊÜôù áðü ðáèïãüíåò 

óõíèÞêåò, ç åðßäñáóç ôçò á-óõíïõêëåÀíçò óôï 

Ýíæõìï ðéèáíþò ðåñéïñßæåôáé, ç õäñïîõëÜóç ôçò ôõñïóßíçò 

äñá áíåîÝëåãêôá êáé õðåñðáñÜãåôáé íôïðáìßíç, ï 

êáôáâïëéóìüò ôçò ïðïßáò óõóóùñåýåé ôïîéêÜ õðïðñïúüíôá 

(åëåýèåñåò ñßæåò), ðïõ ðñïêáëïýí ïîåéäùôéêü stress 

êáé áëëïéþóåéò ôùí êõôôÜñùí. Óôç íüóï Alzheimer, ç áóõíïõêëåÀíç 

óõíáíôÜôáé ùò ç ìç-áìõëïåéäÞò â-ðñüäñïìç 

ðñùôåÀíç (non-amyloid â-component precursor, ÍÁCP), 

óõóôáôéêü ôùí áìõëïåéäþí ðñùôåúíéêþí ðëáêþí ðïõ 

ðáñáôçñïýíôáé óôç íüóï. 18–21 

4. ÓÕÍÏÕÊËÅÚÍÅÓ ÊÁÉ ÐÁÈÏËÏÃÉÁ 

Ïé óõíïõêëåÀíåò åìðëÝêïíôáé óå ìéá óåéñÜ ðïëýðëïêùí 

êáé óïâáñþí íåõñïðáèåéþí êáé Üëëùí íïóçìÜôùí 

êáé óõíïõêëåúíïðÜèåéåò Ý÷ïõí ïíïìáóôåß ìéá óåéñÜ íåõñïåêöõëéóôéêþí 

ðáèÞóåùí, ðïõ Ý÷ïõí êïéíü ÷áñáêôçñéóôéêü 

ôéò åíáðïèÝóåéò ìç äéáëõôÞò á-óõíïõêëåÀíçò åðéëåêôéêÜ 

óå åõðáèåßò ïìÜäåò íåõñéêþí êáé ãëïéáêþí êõôôÜñùí. 

Ïé åíáðïèÝóåéò öÝñåôáé íá åìðïäßæïõí ôç ìåôáêßíçóç 

ôùí ïñãáíéäßùí êáé Üëëùí ðáñáãüíôùí óôï 

êõôôáñüðëáóìá, ìå áðïôÝëåóìá ôçí åðéâñÜäõíóç/áíáóôïëÞ 

ôïõ êõôôáñéêïý ðïëëáðëáóéáìïý êáé ôåëéêÜ ôï 

èÜíáôï ôïõ êõôôÜñïõ. 

Ninkina et al, 1999 40 

Êáñêßíïò ùïèçêþí êáé ðñïíåïðëáóìáôéêÝò ÕðåñÝêöñáóç ðñùôåÀíçò Bruening et al, 200041 âëÜâåò ùïèçêþí 

¢íïéá ìå ó÷çìáôéóìü óùìáôéäßùí Lewy Ó÷çìáôéóìüò áîïíéêþí, óöáéñïåéäþí åíáðïèÝóåùí Galvin et al, 200033 óôçí ïäïíôùôÞ Ýëéêá ôïõ åãêåöÜëïõ 

Íüóïò Parkinson Ó÷çìáôéóìüò áîïíéêþí, óöáéñïåéäþí åíáðïèÝóåùí Galvin et al, 200033 óôçí ïäïíôùôÞ Ýëéêá ôïõ åãêåöÜëïõ 

Íåõñïåêöõëéóìüò ìå óõóóþñåõóç óéäÞñïõ Ó÷çìáôéóìüò áîïíéêþí, óöáéñïåéäþí åíáðïèÝóåùí Galvin et al, 200029 óôïí åãêÝöáëï, ôýðïò 1 óôçí ïäïíôùôÞ Ýëéêá ôïõ åãêåöÜëïõ 

Ôçí ïìÜäá áõôÞ óõíéóôïýí ç íüóïò Alzheimer, ç íüóïò 

Parkinson, ç óêëÞñõíóç êáôÜ ðëÜêáò, ç Üíïéá ìå 

óùìáôßäéá Lewy (Lewy body dementia), ç íüóïò Pick, ç 

áìõïôñïöéêÞ ðëåõñéêÞ óêëÞñõíóç, ï íåõñïåêöõëéóìüò 

ìå óõóóþñåõóç óéäÞñïõ (ôýðïõ 1) êáé ç ôñáõìáôéêÞ 

åãêåöáëéêÞ âëÜâç (ðßí. 1). 

4.1. á-óõíïõêëåÀíç êáé íüóïò ôïõ Parkinson 

Ç íüóïò ôïõ Parkinson áðïôåëåß Ýíá áðü ôá ðëÝïí 

äéáäåäïìÝíá íïóÞìáôá ôïõ íåõñéêïý óõóôÞìáôïò, ðñïóâÜëëïíôáò 

ðïóïóôü >2% ôùí áôüìùí çëéêßáò Üíù ôùí 

65 åôþí. 55 Ç óõ÷íüôçôÜ ôçò áíÝñ÷åôáé óå 4,5–21 ðåñéóôáôéêÜ 

áíÜ 100.000 ðëçèõóìü áíÜ Ýôïò. ×áñáêôçñßæåôáé 

áðü ôçí ýðáñîç åíáðïèÝóåùí ôùí óùìáôéäßùí Lewy 

(Lewy bodies) óôç ìÝëáéíá ïõóßá êáé ôïí åêöõëéóìü êáé 

ôçí áðþëåéá íåõñéêþí êõôôÜñùí óôçí ðåñéï÷Þ ôçò ìÝëáéíáò 

ïõóßáò pars compacta ôïõ åãêåöÜëïõ ôùí áóèåíþí. 

Ôá óùìáôßäéá Lewy ðåñéÝ÷ïõí á-óõíïõêëåÀíç êáé 

åßíáé ÷áñáêôçñéóôéêÜ, áëëÜ ü÷é ðáèïãíùìïíéêÜ, ôçò éäéïðáèïýò 

ìïñöÞò ôçò íüóïõ, êáèþò áðáíôþíôáé êáé óå 

Üëëá íïóÞìáôá. Ïé êëéíéêÝò åêäçëþóåéò ôçò íüóïõ åßíáé 

êõñßùò ôñüìïò ôùí åí çñåìßá ìõþí, âñáäýôçôá åêïõóßùí 

êéíÞóåùí, áêïõóßùò åðéôá÷õíüìåíï âÜäéóìá, éäéüìïñöç 

óôÜóç êáé ìõúêÞ áäõíáìßá. Äåí õðÜñ÷ïõí óõãêåêñéìÝíá 

êñéôÞñéá ðïõ íá ðéóôïðïéïýí áðïëýôùò ôçí 

ýðáñîç ôçò íüóïõ ðñéí áðü ôç äéÜãíùóÞ ôçò, êáèþò ç 

éäéáéôåñüôçôá êáé ç åõáéóèçóßá ôùí óçìåßùí êáé óõìðôùìÜôùí 

ôçò äåí Ý÷ïõí áêüìá åðáêñéâþò áîéïëïãçèåß. 

Ôçò åêäÞëùóçò ôùí óõìðôùìÜôùí ðñïçãåßôáé ðïëõåôÞò 

áóõìðôùìáôéêÞ áðþëåéá íåõñéêþí êõôôÜñùí êáé êáôÜ 

ôçí Ýíáñîç ôçò íüóïõ ðåñßðïõ ôï 80% ôùí íåõñéêþí 

êõôôÜñùí óôéò ðñïóâëçèåßóåò ðåñéï÷Ýò ôïõ åãêåöÜëïõ 

Ý÷ïõí êáôáóôñáöåß, ìå áðïôÝëåóìá ôç óçìáíôéêÞ ìåßùóç 

ôçò íôïðáìßíçò, ôéò áëëïéþóåéò óôá íåõñéêÜ ãÜããëéá 

êáé ôá êéíçôéêÜ óõìðôþìáôá.


Ç åíåñãüò óõììåôï÷Þ ôçò á-óõíïõêëåÀíçò óôçí ðáèïãÝíåóç 

ôçò íüóïõ ôïõ Parkinson, åêôüò áðü ôá óôïé- 

÷åßá ðïõ ðáñáôÝèçêáí ðáñáðÜíù ó÷åôéêÜ ìå ôéò âéï÷çìéêÝò 

ïäïýò óôéò ïðïßåò óõììåôÝ÷åé êáé ðïõ åìðëÝêïíôáé 

óôç íüóï, êáôï÷õñþèçêå ìå äýï ìåôáëëÜîåéò óôï 

ãïíßäéü ôçò (Ala30Pro êáé Ala53Thr), ïé ïðïßåò âñÝèçêáí 

îå÷ùñéóôÜ óå ìéá ìåãÜëç éôáëéêÞ, ìéá ãåñìáíéêÞ 

êáé êÜðïéåò åëëçíéêÝò, ìç óõó÷åôéæüìåíåò ïéêïãÝíåéåò 

ìå ïéêïãåíÞ ìïñöÞ ôçò íüóïõ, 43 óôçí ïðïßá ç íüóïò 

åêäçëþíåôáé ìå åðéêñáôïýóá áõôïóùìéêÞ êëçñïíïìéêüôçôá. 

Óôéò ìïñöÝò áõôÝò ôïõ óõíäñüìïõ, ç ìåôáëëáãìÝíç 

á-óõíïõêëåÀíç áðïôåëåß ôï âáóéêü óõóôáôéêü ôùí 

óùìáôéäßùí Lewy óôç ìÝëáéíá ïõóßá. Ïé óõãêåêñéìÝíåò 

ìåôáëëÜîåéò öáßíåôáé üôé åðçñåÜæïõí óçìáíôéêÜ ôçí Ýìöõôç 

éêáíüôçôá ôçò á-óõíïõêëåÀíçò ãéá ðïëõìåñéóìü. 9 

¢ëëïé ðïëõìïñöéóìïß ôçò á Þ ôùí õðïëïßðùí óõíïõêëåúíþí 

äåí Ý÷ïõí ìÝ÷ñé ôþñá åíï÷ïðïéçèåß ãéá êëçñïíïìéêÝò 

ìïñöÝò ôçò íüóïõ. 

Ìå áöåôçñßá ôï ðáñáðÜíù ãåãïíüò, ïé Saha et al 56 

Ýäåéîáí üôé ç õðåñÝêöñáóç ôçò á-óõíïõêëåÀíçò óôçí 

êáíïíéêÞ áëëÜ êáé ìåôáëëáãìÝíç ìïñöÞ ôçò (Ala53Thr 

Þ Ala30Pro) ðñïêáëåß ôï èÜíáôï ôùí íåõñéêþí êõôôÜñùí 

óôá ïæþäç êáé áéóèçôéêÜ ãÜããëéá êõôôáñéêþí óåéñþí. 

Ï êõôôáñéêüò èÜíáôïò åßíáé áðïðôùôéêüò êáé Ýôóé 

ìüñéá ðïõ óõììåôÝ÷ïõí óå áõôüí ôï ìç÷áíéóìü (Bcl- 

XL) ìåãåèýíïõí ôï áðïôÝëåóìá ôçò õðåñÝêöñáóçò ôçò 

ðñùôåÀíçò, åíþ êÜðïéá Üëëá ìüñéá ðïõ äñïõí áíáóôáëôéêÜ 

(Bad, Bax) ìåéþíïõí ôï áðïôÝëåóìá ôçò äñÜóçò 

ôçò. Ðáñüìïéåò Ýñåõíåò óå êõôôáñéêÝò óåéñÝò ðñïåñ÷üìåíåò 

áðü ôïí éððüêáìðï (H19-7) êáé ðñùôïãåíÞ íåõñéêÜ 

êýôôáñá ôïõ öëïéïý ôïõ åãêåöÜëïõ Ýäåéîáí üôé ç 

á-óõíïõêëåÀíç åíåñãïðïéåß ôoí áðïðôùôéêü ìç÷áíéóìü 

ôùí êõôôÜñùí êáé ðñïêáëåß ôï ó÷çìáôéóìü óùìáôéäßùí 

Lewy óôï êõôôáñüðëáóìá. 15,22 

Åðßóçò, ç õðåñÝêöñáóç ôçò á-óõíïõêëåÀíçò ðñïêáëåß 

ôçí åìöÜíéóç ôùí êýñéùí âéï÷çìéêþí åêäçëþóåùí 

ôïõ ðáñêéíóïíéêïý óõíäñüìïõ, ü÷é ìüíï óôéò êõôôáñéêÝò 

óåéñÝò, áëëÜ êáé óå åñãáóôçñéáêÜ ðåéñáìáôüæùá 

(Drosophila, C57 6J/B åðßìõåò) ðïõ ÷ñçóéìåýïõí ùò 

ìïíôÝëá ôïõ íïóÞìáôïò. 18,57,58 ¸ôóé, ïé óõãêåêñéìÝíïé ïñãáíéóìïß, 

üôáí âñåèïýí êÜôù áðü óõíèÞêåò ðáñüìïéåò 

ìå áõôÝò ðïõ åðéêñáôïýí óôç íüóï ôïõ Parkinson (ð.÷. 

õðåñÝêöñáóç ôçò á-óõíïõêëåÀíçò), åìöáíßæïõí ôéò êýñéåò 

ðáèïãåíåôéêÝò åêäçëþóåéò ôçò íüóïõ, ìå ó÷çìáôéóìü 

óùìáôéäßùí Lewy, åíáðïèÝóåéò á-óõíïõêëåÀíçò êáé 

áðþëåéá íôïðáìéíåñãþí êõôôÜñùí. 

Ôá ðáñáðÜíù áðïôåëïýí ôá ðëÝïí óçìáíôéêÜ óôïé- 

÷åßá ãéá ôç óõó÷Ýôéóç ôçò á-óõíïõêëåÀíçò ìå ôç íüóï 

ôïõ Parkinson. Áíôéêáôïðôñßæïõí ôçí ðñïóðÜèåéá ðïë- 

ëþí åñåõíçôéêþí ïìÜäùí íá åíôïðßóïõí ôï ñüëï ôçò 

ðñùôåÀíçò êáé íá áðïóáöçíßóïõí ôïõò ðáèïãåíåôéêïýò 

ìç÷áíéóìïýò ôïõò ïðïßïõò åíåñãïðïéåß. Ç íüóïò ôïõ 

Parkinson, üìùò, äåí áðïôåëåß Ýíá íüóçìá ðïõ åêäçëþíåôáé 

ìüíï ëüãù ãåíåôéêþí ðáñáãüíôùí, ãé’ áõôü 

Üëëùóôå êáé ç ïéêïãåíÞò ìïñöÞ ôçò, ðïõ ðñïêáëåßôáé 

áðü ôï ìåôáëëáãìÝíï ãïíßäéï ôçò á-óõíïõêëåÀíçò, äåí 

áðïôåëåß ðáñÜ ìüíï Ýíá ìéêñü ðïóïóôü óôç óõ÷íüôçôá 

ôçò íüóïõ. 59 

Ðåñéâáëëïíôéêïß ðáñÜãïíôåò åðçñåÜæïõí ôçí åìöÜíéóç 

êáé ôçí ðñüïäï ôçò íüóïõ. Ôá ðåñéóóüôåñá åõñÞìáôá 

áöïñïýí óôç ÷çìéêÞ ïõóßá ñïôåíüíç (rotenone), 

ðïõ áðïôåëåß Ýíá öõóéêü áíáóôïëÝá ôïõ ìéôï÷ïíäñéáêïý 

óõìðëÝãìáôïò 1 êáé ÷ñçóéìïðïéåßôáé åêôåíþò ùò 

óõóôáôéêü ïéêéáêþí ìéêñïâéïêôüíùí. ×ñïíßá åðáöÞ åñãáóôçñéáêþí 

áñïõñáßùí ìå ôçí ïõóßá áõôÞ ðñïêáëåß 

ôçí åêäÞëùóç éóôïëïãéêþí êáé Üëëùí âéï÷çìéêþí êáé 

êëéíéêþí óçìåßùí êáé óõìðôùìÜôùí ôïõ ðáñêéíóïíéêïý 

óõíäñüìïõ, 60 åíþ âñÝèçêå üôé êáé êÜðïéá Üëëá ìéêñïâéïêôüíá 

(DDC, dieldrin, paraquat) åíåñãïðïéïýí ôç äçìéïõñãßá 

åíáðïèÝóåùí á-óõíïõêëåÀíçò. 9 ÌåãÜëåò óõãêåíôñþóåéò 

óéäÞñïõ, ÷áëêïý Þ êõôï÷ñþìáôïò c åðßóçò 

åíéó÷ýïõí ôïí ðïëõìåñéóìü ôçò á-óõíïõêëåÀíçò. 53,61 

Ç Ýñåõíá óôçí ðáèïãÝíåéá ôïõ ðáñêéíóïíéêïý óõíäñüìïõ 

õðÝäåéîå êáé Üëëïõò ðáñÜãïíôåò ðïõ åìðëÝêïíôáé 

óôç óõóóþñåõóç ôùí óùìáôéäßùí Lewy. Ðñüêåéôáé 

ãéá ïñéóìÝíïõò ìïñéáêïýò êáé âéï÷çìéêïýò ìç÷áíéóìïýò, 

ðïõ áí êáé ï öõóéïëïãéêüò ôïõò ñüëïò åßíáé áðáñáßôçôïò 

ãéá ôç ëåéôïõñãßá ôïõ êõôôÜñïõ, áëëïéþóåéò ôïõò 

ïäçãïýí óôç äçìéïõñãßá ôïîéêþí ðñïúüíôùí ìåôáâïëéóìïý 

(åëåýèåñåò ñßæåò) ðïõ åðéöÝñïõí âëÜâåò óôá êýôôáñá, 

ïäçãþíôáò ìåôáîý Üëëùí êáé óôç óõóóþñåõóç 

ôùí óùìáôéäßùí Lewy (åéê. 1). 

ÓõãêåêñéìÝíá, ôï êõôü÷ñùìá c, ôï ïðïßï ìåôáöÝñåé 

çëåêôñüíéá óôá ìéôï÷üíäñéá êáé ìåóïëáâåß óôçí åíåñãïðïßçóç 

ôïõ ìç÷áíéóìïý áðüðôùóçò, üôáí âñåèåß óå 

óõíèÞêåò üîéíïõ ðåñéâÜëëïíôïò óõóóùñåýåôáé óå Üìïñöåò 

ìÜæåò êáé ôï ßäéï ãßíåôáé ìå ôçí á-óõíïõêëåÀíç. 61 

Áí êáé äåí åíôïðßóôçêå ìéá Üìåóç áëëçëåðßäñáóç ìåôáîý 

ôïõò, áíïóïêõôôáñï÷çìéêÝò áíáëýóåéò äåß÷íïõí üôé 

ïé äýï ðñùôåÀíåò åíôïðßæïíôáé óôá ßäéá óùìáôßäéá. Áíôéüîéíåò 

ïõóßåò áðïôñÝðïõí ôç óõóóþñåõóç áõôþí ôùí 

ðñùôåúíéêþí ìáæþí. 

ÁíáöïñéêÜ ìå ôçí ïõìðéêïõéíïðïßçóç (ubiquination), 

ðïõ óõíôåëåßôáé óôá ìéôï÷üíäñéá êáé áöïñÜ óôïí åíäïêõôôáñéêü 

êáôáâïëéóìü ôùí ðñùôåúíþí, ç ðñùôåÀíç ðáñêßíç 

(parkin), ç ïðïßá ó’ áõôüí ôï ìç÷áíéóìü ëåéôïõñãåß 

ùò ëéãÜóç (Å3), åìðëÝêåôáé óôçí ðáèïëïãßá ôçò íüóïõ 

ôïõ Parkinson. 63 ÌåôáëëÜîåéò óôï ãïíßäéü ôçò Ý÷ïõí


Eéêüíá 1. ÄïìÞ ôçò á-óõíïõêëåÀíçò (á) êáé ìïíôÝëï ôïõ ôñüðïõ ðïëõìåñéóìïý ôçò (â). ÁíáöÝñïíôáé ôá óçìåßá ôùí ìåôáëëÜîåùí ðïõ åìðëÝêïíôáé 

óôçí ïéêïãåíÞ ìïñöÞ ôçò íüóïõ. (Ó÷Þìá ðñïóáñìïóìÝíï áðü ôïõò Giasson & Lee, Neuron, 2001). 62 

åíï÷ïðïéçèåß ãéá ìéá ìïñöÞ íüóïõ ôïõ Parkinson ðïõ 

áñ÷ßæåé óôçí ðáéäéêÞ/íåáíéêÞ çëéêßá êáé åìöáíßæåé áõôïóùìéêÞ 

õðïëåéðüìåíç êëçñïíïìéêüôçôá (Autosomal 

Recessive Parkinson’s Disease, ARPD) 26,64 êáé, óõíåðþò, 

õðïäåéêíýïõí Ýíá óçìáíôéêü ñüëï ôçò ïõìðéêïõéíïðïßçóçò 

óôçí áéôéïëïãßá ôïõ ðáñêéíóïíéêïý óõíäñüìïõ. Ìå 

ìéá óåéñÜ ðåéñáìÜôùí, ïé Shimura et al 65 åíôüðéóáí áëëçëåðßäñáóç 

ôçò á-óõíïõêëåÀíçò ìå ôçí ðáñêßíç (åéê. 

2). Ç ðáñêßíç óõììåôÝ÷åé óôïí êáôáâïëéóìü ôçò á-óõíïõêëåÀíçò 

êáé åéäéêÜ ìéáò ãëõêïóõëéùìÝíçò ìïñöÞò 

ôçò, ðïõ óõíáíôÜôáé óå áóèåíåßò ìå ôçí ARPD. ÁëëáãÝò 

óôç ëåéôïõñãßá ôçò ðáñêßíçò, óõíåðþò, ìðïñåß íá 

áíáóôåßëïõí Þ, áëëéþò, íá ôñïðïðïéÞóïõí ôïí êáôáâïëéóìü 

ôçò óõíïõêëåÀíçò, ìå áðïôÝëåóìá ôç äçìéïõñãßá 

åíáðïèÝóåùí. 

Ôá ðáñáðÜíù óôïé÷åßá áðïäåéêíýïõí ôï âáèìü óôïí 

ïðïßï ç á-óõíïõêëåÀíç ìðïñåß íá åðçñåÜóåé êõôôáñéêïýò 

ìç÷áíéóìïýò êáé íá óõíôåëÝóåé óôçí ðáèïãÝíåéá 

ôçò íüóïõ ôïõ Parkinson. Ç äõóêïëßá ìÝ÷ñé óôéãìÞò íá 

áðïóáöçíéóôåß ï ñüëïò ôçò (êáé ðéèáíþò åðßóçò êáé ôçò 

â êáé ôçò ã-óõíïõêëåÀíçò) ïöåßëåôáé óôï üôé ç íüóïò 

åéíáé ðïëõáéôéáêÞ êáé åêäçëþíåôáé ùò áðïôÝëåóìá ðåñéâáëëïíôéêþí 

êáé ãåíåôéêþí ðáñáãüíôùí. 

4.2. á-óõíïõêëåÀíç êáé óêëÞñõíóç êáôÜ ðëÜêáò/Üíïéá 

ìå óùìáôßäéá Lewy 

¼óïí áöïñÜ óôéò Üëëåò äýï ãíùóôÝò óõíïõêëåúíïðÜèåéåò, 

ôç óêëÞñõíóç êáôÜ ðëÜêáò 27 êáé ôçí Üíïéá ìå 

ôçí ýðáñîç óùìáôéäßùí Lewy, 66 ç óõó÷Ýôéóç ìå ôçí áóõíïõêëåÀíç 

ðåñéïñßæåôáé óôïí åíôïðéóìü ôçò óõíïõêëåÀíçò 

óôéò ðáñáôçñïýìåíåò åíáðïèÝóåéò. 

Ç óêëÞñõíóç êáôÜ ðëÜêáò åßíáé Ýíá áíïóïëïãéêÞò 

áéôéïëïãßáò öëåãìïíþäåò íüóçìá, ðïõ ðñïóâÜëëåé ôï 

êåíôñéêü íåõñéêü óýóôçìá êáé ìÝóù áõôïý êáé Üëëá 

óõóôÞìáôá. Ç íüóïò ðñïêáëåß ôçí êáôáóôñïöÞ ôïõ óôñþìáôïò 

ìõåëßíçò óôá íåýñá êáé ÷áñáêôçñßæåôáé áñ÷éêÜ 

áðü áíáóôñÝøéìåò íåõñïëïãéêÝò åêäçëþóåéò, ìå ÷ñïíéêÞ 

áðüóôáóç ìåôáîý ôïõò, ðïõ áêïëïõèïýíôáé áðü ðñïïäåõôéêü 

åêöõëéóìü ôùí íåýñùí. Ç ðáèïãÝíåéÜ ôçò åßíáé 

Üãíùóôç. ÅíáðïèÝóåéò ôçò á-óõíïõêëåÀíçò óå áóèåíåßò 

ìå óêëÞñõíóç êáôÜ ðëÜêáò Ý÷ïõí âñåèåß óôá ïëéãïäåíäñïêýôôáñá, 

ìå ôç ìïñöÞ ãëïéáêþí êõôôáñïðëáóìáôéêþí 

åíáðïèÝóåùí. 22,23,27 

Óôçí Üíïéá ìå óùìáôßäéá Lewy Ý÷ïõí âñåèåß, åêôüò 

ôùí óùìáôéäßùí Lewy, äõóôñïöéêïß êáé Lewy íåõñßôåò, 

êáèþò êáé ù÷ñÜ óùìáôßäéá ðïõ ðåñéÝ÷ïõí á-óõíïõêëåÀíç. 

22,23 Ç íüóïò åßíáé Üãíùóôçò áéôéïëïãßáò, áöïñÜ óôï


Áëõóßäá 

ðïëõ-ïõìðéêïõéíüíçò 

Aëëçëåðßäñáóç ìåôáîý ðáñêßíçò êáé á-óõíïõêëåÀíçò 

Ïìüëïãç 

Ðáñêßíç 

ðåñéï÷Þ IBR 

ïõìðéêïõéíüíçò Äáêôýëéïò ðåñéï÷Þ Äáêôýëéïò 

á-Sp22 

á 

â 

â 

á 

Óýìðëåãìá ðñùôåïóþìáôïò 

26S (PA700 + 20S + PA700) 

ÔìÞìáôá 

ðåðôéäßùí 

E2 

(UbcH7) 

Eéêüíá 2. Ñüëïò ôçò ðáñêßíçò óôï ìç÷áíéóìü oõìðéêïõéíïðïßçóçò. Ç 

ðñùôåÀíç äñá ùò óýíäåóìïò ìåôáîý Üëëùí ìïñßùí ôïõ ìç÷áíéó˝ìïý 

(Å2) êáé ïäçãåß ôéò ðñùôåÀíåò óôï ðñùôåüóùìá ãéá áðïóýíèåó˝ç. á- 

Sp22 åßíáé ìéá ãëõêïóõëéùìÝíç ìïñöÞ ôçò á-óõíïõêëåÀíçò, ðïõ åìöáíßæåôáé 

óôçí APRD êáé áðïôåëåß õðüóôñùìá ôçò ðáñêßíçò. (Ó÷Þìá˝ ðñïóáñìïóìÝíï 

áðü ôïõò Giasson & Lee, Neuron 2001). 62 

Ub 

Ub 

Ðñùôåüóùìá 

20S 

10–20% ôïõ óõíüëïõ ôùí äéáöüñùí åéäþí Üíïéáò êáé 

åêäçëþíåôáé êõñßùò óå ìåãÜëç çëéêßá. Ï ãïíüôõðïò 

ôçò ApoE 4 áðïëéðïðñùôåÀíçò óõíáíôÜôáé óå Ýíôïíï 

âáèìü, üôáí ôï íüóçìá áðáíôÜôáé ìáæß ìå ôç íüóï 

Álzheimer. 

4.3. â-óõíïõêëåÀíç êáé ðáèïëïãßá 

Ãéá ôç â-óõíïõêëåÀíç äåí õðÜñ÷ïõí ðïëëÜ åõñÞìáôá, 

ôüóï ãéá ôï öõóéïëïãéêü ôçò ñüëï, êÜôé ðïõ éó÷ýåé êáé 

ãéá ôéò á êáé ã, áëëÜ ïýôå êáé ãéá ôçí åíåñãü óõììåôï÷Þ 

ôçò óå äéÜöïñá íïóÞìáôá. Ðáñüë’ áõôÜ, óõãêåíôñþóåéò 

ôçò ðñùôåÀíçò äéáðéóôþíïíôáé óå íåõñïëïãéêÝò ðáèÞóåéò. 

29 Óôç íüóï ôïõ Parkinson êáé ôçí Üíïéá ìå óùìáôßäéá 

Lewy åíôïðßæïíôáé óôïõò äõóôñïöéêïýò íåõñßôåò óôïí 

E1 

éððüêáìðï êáé óå Üëëåò ðåñéï÷Ýò ôïõ åãêåöÜëïõ, ìáæß 

ìå ôçí á-óõíïõêëåÀíç. 29 Äåí Ý÷ïõí âñåèåß ðïëõìïñöéóìïß 

ôçò â-óõíïõêëåÀíçò ðïõ íá åíï÷ïðïéïýíôáé ãéá ôçí 

åìöÜíéóç ôùí óõíïõêëåúíïðáèåéþí (ðßí. 2). 

4.4. ã-óõíïõêëåÀíç êáé ðáèïëïãßá 

Ç óõììåôï÷Þ ôçò â êáé ôçò ã-óõíïõêëåÀíçò, áí êáé 

ìç åíåñãüò óôçí ðáèïãÝíåéá ôçò íüóïõ ôïõ Parkinson, 

Ý÷åé äéáðéóôùèåß êáé óå Üëëá íåõñïåêöõëéóôéêÜ íïóÞìáôá. 

29 Åðßóçò, õðÜñ÷åé óçìáíôéêÞ âéâëéïãñáößá ó÷åôéêÜ 

ìå ôçí åìðëïêÞ ôçò ã-óõíïõêëåÀíçò óå êáêïÞèåéò 

íåïðëáóßåò, êõñßùò óôïí êáñêßíï ôïõ ìáóôïý êáé ôùí 

ùïèçêþí (ðßí. 3). 

×áñáêôçñéóôéêü ãéá ôç ã-óõíïõêëåÀíç åßíáé üôé ç ðñùôåÀíç 

÷áñáêôçñßóôçêå óõã÷ñüíùò áðü 3 äéáöïñåôéêÝò 

ïìÜäåò, ïé ïðïßåò ÷ñçóéìïðïßçóáí äéáöïñåôéêü ôñüðï 

ãéá ôçí áðïìüíùóç ôïõ ãïíéäßïõ. ¸ôóé, ìéá ïìÜäá ïíüìáóå 

ôï ãïíßäéï ùò ãïíßäéï ãéá ôçí åéäéêÞ ãéá ôïí êáñêßíï 

ôïõ ìáóôïý ðñùôåÀíç (breast cancer specific gene, 

BCSG), 39 ç äåýôåñç ùò ãïíßäéï ãéá ôçí ðåñéöåñéêÞ, 

ðáñüìïéá ìå óõíïõêëåÀíç ðñùôåÀíç 67 êáé ç ôñßôç ùò ãóõíïõêëåÀíç. 

17 Óôçí ïõóßá, ðñüêåéôáé ãéá ôçí ßäéá ðñùôåÀíç, 

ç ïðïßá, üðùò áíáöÝñåôáé êáé ðáñáêÜôù, ðáñïõóéÜæåé 

ìåãÜëá ðïóïóôÜ Ýêöñáóçò óôïí êáñêßíï ôïõ ìáóôïý. 

Ïé ðåñéï÷Ýò Ýêöñáóçò ôçò ã-óõíïõêëåÀíçò åíôïðßóôçêáí 

ìå éóôïëïãéêÝò áíáëýóåéò óôá êéíçôéêÜ íåõñþíéá 

ôùí ïöèáëìïêéíçôéêþí êáé ôñéäõìéêþí êéíçôéêþí 

ðõñÞíùí, êáèþò êáé óôçí ðáñåãêåöáëßäá, ôï èÜëáìï, 

ôïí õðïèÜëáìï, ôïí ïöèáëìéêü âïëâü êáé ôïí éððüêáìðï. 

Ç ðñùôåÀíç ðáñïõóéÜæåé ìÝãéóôï âáèìü Ýêöñáóçò 

êáôÜ ôçí ðåñßïäï ôçò áíÜðôõîçò ôùí íåõñáîüíùí. 17 

Óå êõôôáñéêÝò óåéñÝò üðïõ õðåñåêöñÜæåôáé ç ã-óõíïõêëåÀíç 

ðñïêáëåßôáé ôñïðïðïßçóç ôïõ êõôôáñïóêåëåôïý. 

ÓõãêåêñéìÝíá, ðáñáôçñåßôáé äñáóôéêÞ ìåßùóç ôùí 

3 íåõñïíçìáôßùí (NF-H, NF-M, NF-L), ìÝóù ôùí áóâåóôéï-åîáñôþìåíùí 

ðñùôåáóþí, åíþ äåí åðçñåÜæïíôáé 

Üëëá ìÝñç ôïõ êõôôáñïóêåëåôïý. 

Ïé Ji et al 39 Ýäåéîáí üôé ç ã-óõíïõêëåÀíç åêöñÜæåôáé 

óå íåïðëáóìáôéêÜ åðéèçëéáêÜ êýôôáñá ôïõ ìáóôïý, óå 

Ýíôáóç áíÜëïãç ôïõ âáèìïý êáêïÞèåéáò, äçëáäÞ ôçò 

åðéèåôéêüôçôáò ôïõ êáñêßíïõ, åíþ äåí åêöñÜæåôáé óå 

õãéÞ éóôü Þ óå êáëïÞèåéò ìïñöÝò íåïðëáóéþí êáé åîáéôßáò 

áõôïý áñ÷éêÜ åß÷å ÷áñáêôçñéóôåß ùò ðñùôåúíéêüò 

äåßêôçò ãéá ôïí êáñêßíï ôïõ ìáóôïý. Åðßóçò, ïé Âruening 

et al 41 Ýäåéîáí üôé ç ã-óõíïõêëåÀíç åêöñÜæåôáé óå ðïóïóôü 

20% êáé óå ðñïíåïðëáóìáôéêÝò åíáðïèÝóåéò óôéò 

ùïèÞêåò.


Ç óõììåôï÷Þ ôçò ã-óõíïõêëåÀíçò óôïõò ìç÷áíéóìïýò 

áýîçóçò êáé ìïñöïëïãßáò ôùí íåõñáîüíùí êáé óôçí 

áêåñáéüôçôá ôïõ óêåëåôïý ôïõ êõôôÜñïõ, êáèþò êáé ç 

ÝêöñáóÞ ôçò óôéò åðéèåôéêÝò êáé ìåôáóôáôéêÝò ìïñöÝò 

êáñêßíïõ, åíäÝ÷åôáé íá áöïñïýí óå êïéíïýò ìç÷áíéóìïýò, 

ïé ïðïßïé ôñïðïðïéïýíôáé áíÜëïãá ìå ôéò óõíèÞêåò 

êáé åìðëÝêïíôáé óôçí ðáèïãÝíåéá íüóùí. ÐñïêåéìÝíïõ 

íá åîáêñéâùèåß åÜí ç ýðáñîç ôçò ã-óõíïõêëåÀíçò 

ðñïäéáèÝôåé óôçí åìöÜíéóç êáñêßíïõ Þ íåõñïëïãéêþí 

ðáèÞóåùí (íüóïò Alzheimer, íüóïò Parkinson), åñåõíÞèçêáí 

ãåíåôéêïß ðïëõìïñöéóìïß êáé ìåôáëëÜîåéò óôï ãïíßäéü 

ôçò, áëëÜ äåí åîáêñéâþèçêå Ýíáò ìåôñÞóéìïò êáé 

óôáèåñüò ðáñÜãïíôáò ðïõ íá äéêáéïëïãåß ìéá óõó÷Ýôéóç. 

39,51 

5. ÌÏÍÔÅËÏ ÁËËÇËÅÐÉÄÑÁÓÇÓ ÓÕÍÏÕÊËÅÚÍÙÍ – 

ÓÕÌÐÅÑÁÓÌÁÔÁ 

Ìéá èåùñßá ðïõ êåñäßæåé óõíå÷þò Ýäáöïò óôïí ôïìÝá 

ôçò Ýñåõíáò ó÷åôéêÜ ìå ôéò óõíïõêëåÀíåò, åßíáé üôé ïé 3 

ðñùôåÀíåò âñßóêïíôáé óå ìéá äõíáìéêÞ éóïññïðßá. ÌåëÝôåò 

ôùí Rockenstein et al 56 áíáöïñéêÜ ìå ôçí Ýêöñáóç 

ôùí ðñùôåúíþí Ýäåéîáí üôé ç â-óõíïõêëåÀíç åßíáé ðïóïôéêÜ 

ðåñéóóüôåñç, áêïëïõèïýìåíç áðü ôç ã êáé ôçí á. Ïé 

ßäéïé åðéóôÞìïíåò åîÝôáóáí ôá ó÷åôéêÜ ðïóïóôÜ ôùí ðñùôåúíþí 

óôïí áíþôåñï êñïôáöéêü öëïéü ôïõ åãêåöÜëïõ, 

ìéá ðåñéï÷Þ ðïõ ðñïóâÜëëåôáé éäéáßôåñá óå áóèåíåßò ìå 

ôç íüóï Alzheimer êáé ôçí Üíïéá ìå óùìáôßäéá Lewy, êáé 

ôá óõíÝêñéíáí ìå ôá áíôßóôïé÷á ðïóïóôÜ õãéþí áôüìùí. 

Äéáðßóôùóáí üôé, óôçí ðåñßðôùóç ôçò íüóïõ Alzheimer, 

ôá ðïóïóôÜ ôçò â-óõíïõêëåÀíçò ìåéþèçêáí, ôçò ã áõîÞèçêáí, 

åíþ ôçò á ðáñÝìåéíáí óôáèåñÜ. Óôçí Üíïéá ìå 

óùìáôßäéá Lewy, ç ã-óõíïõêëåÀíç ðáñÝìåéíå óôáèåñÞ, ç 

á áõîÞèçêå êáé ç â ìåéþèçêå. ¸ñåõíåò åðßóçò äåß÷íïõí 

üôé ç óõíôïíéóìÝíç Ýêöñáóç ôùí á êáé â-óõíïõêëåúíþí 

ðáßæåé ñüëï êáé êáôÜ ôç äéáöïñïðïßçóç ôùí áéìïðåôáëßùí. 

Óå Üëëåò åñãáóßåò äéáðéóôþèçêå üôé åíþ ïé 3 óõíïõêëåÀíåò 

Ý÷ïõí ôéò ßäéåò âéïöõóéêÝò éäéüôçôåò, ç á åßíáé 

öõóéêÜ ðåñéóóüôåñï åðéññåðÞò óôïí éíéäéóìü óå ó÷Ýóç 

ìå ôéò Üëëåò äýï 58 êáé –áêüìç ðåñéóóüôåñï åíäéáöÝñïí– 

üôé ç â êáé ç ã ìðïñïýí íá áðïôñÝøïõí ôï ó÷çìáôéóìü 

éíéäßùí ôçò á-óõíïõêëåÀíçò. ÓõãêåêñéìÝíá, âñÝèçêå 

üôé ðëÞñçò áðïôñïðÞ ó÷çìáôéóìïý éíéäßùí ìðïñåß 

íá åðéôåõ÷èåß óå ìïñéáêÞ óõãêÝíôñùóç 4:1 ôçò â ùò 

ðñïò ôçí á-óõíïõêëåÀíç, ÷ùñßò ç â íá åíóùìáôþíåôáé 

óôá ó÷çìáôéæüìåíá éíßäéá. Óå in vivo óõíèÞêåò, ïé 

Hashimoto et al 61 Ýäåéîáí üôé ç â-óõíïõêëåÀíç ìðïñåß 

íá áðïôñÝøåé ôïí éíéäéóìü ôçò á-óõíïõêëåÀíçò óôïí 

åãêÝöáëï äéáãåíåôéêþí ðïíôéêéþí, êáèþò êáé óå ìç 

íåõñéêÝò êõôôáñéêÝò óåéñÝò ðïõ åêöñÜæïõí ôçí á-óõíïõêëåÀíç. 

Ìå âÜóç ôá ðáñáðÜíù, ðáèÞóåéò üðùò ç 

íüóïò ôïõ Parkinson ìðïñïýí íá èåùñçèïýí ùò ðïëõáéôéáêÝò 

êáé ï ðïëõìåñéóìüò ôçò á-óõíïõêëåÀíçò ùò 

ôï êïéíü óýìðôùìá ôçò åðßäñáóçò åíäïãåíþí êáé ðåñéâáëëïíôéêþí 

ðáñáãüíôùí. Ôá ó÷åôéêÜ åðßðåäá ôçò â êáé 

ã-óõíïõêëåÀíçò åíäÝ÷åôáé íá åßíáé ïé åíäïãåíåßò ðáñÜãïíôåò. 

Ïé Uversky et al 58 åéêÜæïõí üôé ç â êáé ç ãóõíïõêëåÀíç 

ìðïñåß íá óôáèåñïðïéïýí Ýíáí åíäéÜìåóï 

ó÷çìáôéóìü ôçò á-óõíïõêëåÀíçò, ðïõ ïäçãåß óå Üìïñöïõò 

áíôß ãéá éíþäåéò ó÷çìáôéóìïýò^ êÜôù áðü ðáèïëïãéêÝò 

óõíèÞêåò áõôÞ ç éóïññïðßá äéáôáñÜóóåôáé êáé 

ðáñÜãïíôáé éíßäéá. Êáèþò áõôÞ ç èåùñßá äåí óôçñßæåôáé 

óå åðéóôçìïíéêÜ åõñÞìáôá ïýôå Ý÷åé âñåèåß ðïéï åßíáé 

ôï ôïîéêü åßäïò ðïõ ðñïêáëåß ôï èÜíáôï ôùí íåõñéêþí 

êõôôÜñùí, äåí ìðïñåß íá áðïêëåéóôåß ôï åíäå÷üìåíï ç 

ôïîéêüôçôá íá ðñïÝñ÷åôáé áðü áõôüí ôïí åíäéÜìåóï ó÷çìáôéóìü, 

ðïõ óôáèåñïðïéåßôáé áðü ôéò â êáé ôéò ã-óõíïõêëåÀíåò. 

ÊÜôé ôÝôïéï óçìáßíåé üôé ôá õøçëÜ ðïóïóôÜ 

ôçò â êáé ã-óõíïõêëåÀíçò áðïôåëïýí ðáèïãüíï ðáñÜãïíôá. 

Ôá ðáñáðÜíù óôïé÷åßá äßíïõí ìéá åéêüíá ãéá ôï åßäïò 

ôùí åñåõíþí ðïõ äéåîÜãïíôáé óôïí ôïìÝá ôçò ìïñéáêÞò 

íåõñïåðéóôÞìçò üóïí áöïñÜ óôéò óõíïõêëåÀíåò 

êáé ðáñáèÝôåé ôá êõñéüôåñá ìÝ÷ñé ôþñá åðéôåýãìáôÜ ôïõò. 

Ç êáôáíüçóç ôùí âéï÷çìéêþí ïäþí êáé ôçò ãåíåôéêÞò 

åðßäñáóçò óôçí åìöÜíéóç êáé åîÝëéîç ôùí íåõñïåêöõëéóôéêþí 

íüóùí Ý÷åé ðñùôåýïíôá ñüëï óôçí ðñïóðÜèåéá 

ðñüëçøçò, äéÜãíùóçò êáé èåñáðåßáò áõôþí ôùí ðáèÞóåùí. 

Ç ëåéôïõñãßá ôùí óõíïõêëåúíþí ðñùôåúíþí êáé ç 

óõììåôï÷Þ ôïõò óôéò ðáèïãüíåò äéáäéêáóßåò, üðùò Ý÷åé 

õðïäåßîåé ç Ýñåõíá óå ðåéñáìáôéêÜ ìïíôÝëá íïóçìÜôùí 

óå äéáãåíåôéêïýò ïñãáíéóìïýò, 18,24,56,57,68 áðïôåëåß âáóéêü 

êïììÜôé ôçò ðáèïöõóéïëïãßáò êáé ç ðñïóðÜèåéá êáôáíüçóçò 

ôïõ ñüëïõ ôïõò ïñßæåôáé áðü ôçí áíÜãêç åýñåóçò 

íÝùí èåñáðåõôéêþí ïäþí ãéá ðáèÞóåéò ðïõ ðñïóâÜëëïõí 

ìåãÜëï ìÝñïò ôïõ ðëçèõóìïý ôùí äõôéêþí 

êïéíùíéþí 

Ç ìåëÝôç ôùí óõíïõêëåúíþí áíáìÝíåôáé íá äéáäñáìáôßóåé 

ðïëý óçìáíôéêü ñüëï, êáèþò ôï ðëÞèïò ôùí 

íïóçìÜôùí óôá ïðïßá åìðëÝêïíôáé êáé ôá óôïé÷åßá ãéá 

ôç óõíôïíéóìÝíç Ýêöñáóç ôùí ôñéþí ìåëþí ôçò ïéêïãÝíåéáò 

õðïäçëþíïõí ìéá åõñýôåñç óõììåôï÷Þ ôïõò óôç 

öõóéïëïãßá ôïõ êõôôÜñïõ. Ç áðïóáöÞíéóç áõôþí ôùí 

ìç÷áíéóìþí áðïôåëåß óôü÷ï êáé ìÝóï ãéá ôçí êáôáíüçóç 

ôçò ðáèïãÝíåóçò ôùí íïóçìÜôùí üðïõ åìðëÝêïíôáé.


ABSTRACT 

................................................................................................................................................................................ 

Synucleins: Íew prospects in the diseases of the nervous system 

K. PAPACHRONI, 1 A. PAPADIMITRIOU, 2 A. KALOFOUTIS 1 

1Department of Biological Chemistry, University of Athens, Medical School, 

2Department of Neurology, University of Larissa, Medical School, Larissa, Greece 

Archives of Hellenic Medicine 2003, 20(6):643–653 

Research in the molecular neuroscience field in the last years has revealed a family of proteins called synucleins, 

present in abundance in the nervous system. Synucleins are small, heat-stable and soluble proteins with a 

characteristic hydrophobic stretch of 5 to 6 highly conserved, imperfect repeats within the N-terminal. The 

developmental expression pattern of á and â-synucleins is similar to that of synaptobrevin and synaptophysin, 

two synaptic proteins with an established and well-characterised role in the physiology of the nervous system 

and in the development and maturation of synapses in the brain. Regarding the physiological function of 

synucleins there is substantial evidence that they are involved in the development of the synapses in the brain, 

in the recycling of the neuro-transmitters (NTs) vesicles, and the regulation of the relative concentrations of the 

NTs in the synapses, as well as in the mechanisms of cellular communication. However there is no unified and 

well-characterised model that describes the physiological function of synucleins and their specific role in the 

physiology of the cell. The various findings come from studies that have examined the proteins under different 

experimental conditions and thus they are sometimes contradictory. Although the physiological function of 

synucleins remains elusive, an abundance of studies has examined the relationship of these proteins with a 

range of neurological and other diseases, especially neurodegenerative diseases and cancer. A group of neurodisorders 

has been named synucleinopathies, as they are characterised by proteinaceous inclusions in the brains 

of the patients whose main constituent is á-synuclein. This group includes Alzheimer’s disease, Parkinson’s 

disease and multiple sclerosis. This review provides an account of the knowledge about the physiological 

function of synucleins and describes their implication with pathological conditions, giving specific emphasis on 

Parkinson’s disease. 

................................................................................................................................................................................ 

Key words: Alzheimer’s disease, Multiple sclerosis, Parkinson’s disease, Ñroteins 14-3-3, Synucleins á, â, ã 

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Corresponding author: 

A. Kalofoutis, Department of Biological Chemistry, University 

of Athens, Medical School, Laboratory Buildings, 75 M. 

Asias street, GR-115 27 Athens, Greece

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