Program 2011 - Neurowissenschaftliche Gesellschaft eV - MDC

Symposia
Symposia
SYMPOSIUM 6, THURSDAY, MARCH 24, 9:00 - 12:00
Introductory Introductory Remarks Remarks to to Symposium Symposium 6
6
Motor Motor neuron neuron disease disease models: models: models: Loss
Loss
of of function function or or gain gain gain of of of toxic toxic function? function?
function?
Molecular Molecular mechanisms mechanisms mechanisms and and
and
therapeutic therapeutic perspectives
perspectives
Albrecht M. Clement and Christian Behl, Mainz
Spinal muscular atrophy (SMA) and amyotrophic lateral
sclerosis (ALS) are detrimental neurodegenerative disorders
and characterized by the specific loss of motor neurons in
the spinal cord. A key for understanding their aetiology is
the identification of genes involved in disease pathogenesis
and the generation of useful experimental models. Although
the underlying molecular mechanisms of motor neuronspecific
degeneration are still largely unknown, recent studies
have significantly advanced our understanding of the genetics
as well as molecular and cellular processes correlated with
disease pathogenesis. In particular the identification of two
new ALS-genes TDP-43 and FUS, both are DNA/RNAbinding
proteins, turned the spot light on impaired RNA
processing as one possible fundamental pathomechanism
in ALS in addition to protein aggregation and oxidative
stress. Interestingly, SMA is caused by a reduced expression
of „survival motor neuron“ (SMN), a protein involved in
mRNA splicing.
The aim of this symposium is to highlight our current
understanding of motor neuron disease ranging from
advances in molecular biology and genetics to therapeutic
perspectives. Firstly, Ammar Al-Chalabi will discuss the
search for new genes involved in familial forms of ALS but
also the genetic influence in sporadic ALS, which represents
more than 90 % of all cases. On this line, the identification
of susceptibility markers and/or modifiers of familial forms
might shed light on the aetiology of sporadic ALS, which
Wim Robberecht is interested in by using zebrafish models
for ALS.
In the second part of the symposium the speakers will discuss
new insight on the pathomechanisms of familial forms of
motor neuron disease. Albrecht Clement will present recent
advances in understanding mutant SOD1 toxicity by
analysing the biochemical properties and detrimental action
of obligate SOD1-dimer proteins in cellular and C. elegans
disease models. Manuela Neumann and Michael Sendtner
have largely contributed to the current view that impaired
RNA-processing might significantly contribute to ALS and
SMA pathogenesis, respectively. The generation of new TDP-
43 mouse models for ALS will be discussed as well as the
fundamental biochemical and cell physiological processes
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