Clusterin
Clusterin together for a cure
Astrocytes are the most abundant cell in the central nervous system, outnumbering neurons several times over. They are integral for normal brain development and functioning: providing neuronal trophic support, the ability to form synapses (the connections between neurons), and importantly they are involved in synapse pruning and refinement. Early in disease, astrocytes become ‘reactive’ a dysfunctional/disease state in which they lose most normal astrocyte functions, and can switch to multiple reactive states. One type of reactive astrocyte that is common in many neurodegenerative diseases releases a potent neurotoxin, driving destruction of synapses and neurons. We are interested in knowing what effect disease-associated mutations have on normal astrocyte function, as recent GWAS studies hint at the fact that disease-causing mutations occur in genes that are highly expressed by astrocytes. One of these genes, CLU (clusterin/apolipoprotein J), is highly expressed by astrocytes, and associated with cellular debris clearance and apoptosis and several GWAS studies implicate it as a risk allele in Alzheimer’s disease. Here we will investigate the role of mutated CLU in driving astrocyte dysfunction.
IN COLLABORATION WITH:
Paul Frazel, NYU Langone Health
Shane A. Liddelow, PhD, NYU Langone Health