School of Medicine & Public Health
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- Chiu Lab
Mitochondria in Neurogenerative Diseases
Mitochondria supply energy to maintain health of the nervous system. Our laboratory is interested in how mitochondrial dysfunction contributes to neurodegenerative diseases. In normal neurons, mitochondria are targeted to dendritic, axonal and synaptic compartments to maintain proper signaling in brain network. We are interested in how mitochondria are targeted to various neuronal compartments, and how inappropriate targeting contributes to pathology. Currently we are interested in the role of a key anchoring protein, Syntaphilin (SNPH), in the demyelinating disease multiple sclerosis (MS). MS is the most devastating of all demyelinating diseases in the US, affecting 10-20 per 100,000. MS typically has two phases: early Relapsing-Remitting MS (RRMS) with robust inflammation that transitions into a Secondary Progressive MS (SPMS) with subdued inflammation. Progressive MS poses the single most important treatment challenge to MS: once MS converts into the progressive phase, neurodegeneration essentially becomes irreversible and resists virtually all approved FDA treatments. The key to treating late phase MS lies in the elucidation of a non-inflammatory mechanism for killing nerve tissues. Using animal models for Progressive MS, we discovered that excessive anchoring of mitochondria by SNPH underlies neuronal death and that genetic knockout of SNPH leads to dramatic neuroprotection. Our ultimate goal is to design a therapeutic treatment for Progressive MS by targeting SNPH to unclog damaging congestion of mitochondria in this terminal phase of MS.