Neuroprotective role of the ER co-chaperone SIL1 in human neurodegenerative disease
Abnormal accumulations of misfolded proteins that elicit endoplasmic reticulum (ER) stress are major pathological hallmarks of neurodegenerative disease such as Alzheimer´s disease, Parkinson´s disease, and Amyotrophic lateral sclerosis (ALS). Mutations in the ER co-chaperon SIL1 cause Marinesco-Sjögren-Syndrome, which is characterized clinically by cerebellar degeneration, cataracts, and vacuolar myopathy. Research teams from Aachen, Munich, Amsterdam and Bern recently reported in joint publications that SIL1 mutation leads to peculiar ER alterations in patients and mice and that SIL1 regulates motor neuron subtype-selective ER stress in ALS. Results obtained with G93A-SOD1 transgenic ALS mice suggest that SIL1 protects neurons from ER stress and ER stress induced autophagy. These findings suggest that SIL1 could be a therapeutic target in motor neuron diseases and other neurodegenerative disorders.
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Krieger M, Roos A, Stendel C, Claeys KG, Sonmez FM, Baudis M, Bauer P, Bornemann A, de Goede C, Dufke A, Finkel RS, Goebel HH, Häussler M, Kingston H, Kirschner J, Medne L, Muschke P, Rivier F, Rudnik-Schöneborn S, Spengler S, Inzana F, Stanzial F, Benedicenti F, Synofzik M, Lia Taratuto A, Pirra L, Tay SK, Topaloglu H, Uyanik G, Wand D, Williams D, Zerres K, Weis J, Senderek J. SIL1 mutations and clinical spectrum in patients with Marinesco-Sjogren syndrome. Brain. 136(Pt 12): 3634-44, 2013