accepted manuscript

ACCEPTED MANUSCRIPT
dopaminergic neurons. These neurons are characterized by a high oxidative burden
resulting from dopamine metabolism and excitotoxicity, while their antioxidative
repertoire is rather limited (rev. in [18, 82]). In this context it is interesting to note that
regiospecific differences in biochemical and structural parameters of brain
mitochondria have been documented. Another key player seems to be calcium. Adult
dopaminergic neurons are uniquely dependent on voltage-dependent L-type Ca 2+
channels for autonomous pacemaking activity [314-317]. In keeping with a crucial
role of mitochondria in regulating calcium homeostasis, a dysbalance in calcium
buffering seems to be causally related to the selective degeneration of dopaminergic
neurons (rev.in [318]).
Collectively, the exceptional physiological features of dopaminergic neurons
help to explain why mitochondrial fidelity and an effective cellular quality control
and stress response management are paramount to the survival of these neurons,
particularly in an aging individual. There is compelling evidence that at least some of
the PD-associated genes interface with these pathways . It will now be a challenging
endeavour to exploit these pathways as a rationale to halt or delay disease progression
and to move basic research into clinical practice.
ACCEPTED MANUSCRIPT
37