The Chandra lab explores two related themes, those of synapse loss and neurodegeneration. Synapse loss is an early, defining event in neurodegenerative diseases, such as Parkinson's disease. In these prolonged diseases, decreases in synapse density are the best correlates of disease progression. Yet, little is known about the pathways that maintain synapses and their roles in aging and neurodegeneration. We are characterizing a novel presynaptic mechanism for the prevention of synapse loss and neurodegeneration involving the co-chaperone cysteine string protein α (CSPα). We are also screening for new synapse maintenance genes using a dissociated neuronal culture system.
Parkinson's disease (PD) is a prevalent, neurodegenerative disease with strong genetic underpinnings. The first PD gene to be identified was the α-synuclein gene. Three point mutations and gene multiplications link α-synuclein to familial PD. In addition, α-synuclein protein is the main component of Lewy bodies, the pathological signature for PD. We are elucidating both the physiological functions and pathological properties of α-synuclein, in an effort to understand its central role in PD. Our lab uses mouse genetics in combination with biochemical, biophysical, and cell biological approaches to tackle these important questions.