Distal hereditary motor neuropathy
The distal hereditary motor neuropathies (dHMN) are a group of dominant, recessive or X-linked motor axonopathies, most often starting in youth or early adulthood, that are slowly progressive in nature. They have many similarities to Charcot-Marie-Tooth disease (CMT) but have, by definition, no sensory involvement. There are many different forms of dHMN (http://neuromuscular.wustl.edu). Their pathogenesis is poorly understood and no treatment is available.
Project: Heat shock proteins in the pathogenesis of dHMN
Investigator: Ludo Van Den Bosch
We have previously identified mutations in the gene encoding HSPB1 (HSP27) to cause dHMN. HSP27 is an ATP-independent heat shock protein that has anti-apoptotic and chaperoning activity, but whose exact mechanism of action is far from understood. In the neuron, it is present in the axon, but how mutations can give rise to a dominant axonal neuropathy is unknown. In the present project, we investigate the pathogenesis of the axonopathy induced by HSP27 mutations and explore the cellular actions of this protein in neurons and glial cells.
|
|
REFERENCES
1. Lambrechts D, Robberecht W, Carmeliet P. Heterogeneity in motoneuron disease. Trends Neurosci 2007;30(10):536-44.
2. Van Damme P, Braeken D, Callewaert G, Robberecht W, Van Den Bosch L. GluR2 deficiency accelerates motor neuron degeneration in a mouse model of amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 2005;64(7):605-12.
3. Van Damme P, Bogaert E, Dewil M, et al. Astrocytes regulate GluR2 expression in motor neurons and their vulnerability to excitotoxicity. Proc Natl Acad Sci U S A 2007;104(37):14825-30.
4. van Es MA, Van Vught PW, Blauw HM, et al. ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study. Lancet Neurol 2007;6(10):869-77.
5. Lemmens R, Van Hoecke A, Hersmus N, et al. Overexpression of mutant superoxide dismutase 1 causes a motor axonopathy in the zebrafish. Hum Mol Genet 2007;16(19):2359-65.
6. Sleegers K, Brouwers N, Maurer-Stroh S, et al. Progranulin genetic variability contributes to amyotrophic lateral sclerosis. Neurology 2008;71(4):253-9.
7. Van Damme P, Van Hoecke A, Lambrechts D, et al. Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival. J Cell Biol 2008;181(1):37-41.
|
Research 
