PT  - JOURNAL ARTICLE
AU  - Dinesh C. Joshi
AU  - Chuan-Li Zhang
AU  - Tien-Min Lin
AU  - Anchal Gusain
AU  - Melissa G. Harris
AU  - Esther Tree
AU  - Yewin Yin
AU  - Connie Wu
AU  - Zu-Hang Sheng
AU  - Robert J Dempsey
AU  - Zsuzsanna Fabry
AU  - Shing Yan Chiu
TI  - Deletion of Mitochondrial Anchoring Protects Dysmyelinating Shiverer: Implications for Progressive MS
AID  - 10.1523/JNEUROSCI.3859-14.2015
DP  - 2015 Apr 01
TA  - The Journal of Neuroscience
PG  - 5293--5306
VI  - 35
IP  - 13
4099  - http://www.jneurosci.org/content/35/13/5293.short
4100  - http://www.jneurosci.org/content/35/13/5293.full
SO  - J. Neurosci.2015 Apr 01; 35
AB  - The demyelinating disease multiple sclerosis (MS) has an early inflammatory phase followed by an incurable progressive phase with subdued inflammation and poorly understood neurodegenerative mechanism. In this study, we identified various parallelisms between progressive MS and the dysmyelinating mouse model Shiverer and then genetically deleted a major neuron-specific mitochondrial anchoring protein Syntaphilin (SNPH) from the mouse. Prevailing evidence suggests that deletion of SNPH is harmful in demyelination. Surprisingly, SNPH deletion produces striking benefits in the Shiverer by prolonging survival, reducing cerebellar damage, suppressing oxidative stress, and improving mitochondrial health. In contrast, SNPH deletion does not benefit clinical symptoms in experimental autoimmune encephalomyelitis (EAE), a model for early-phase MS. We propose that deleting mitochondrial anchoring is a novel, specific treatment for progressive MS.