Clusterin

Clusterin (CLU) is a 52.5 kDa secreted and intracellular protein that functions as an extracellular chaperone preventing aggregation of misfolded proteins (UniProt: P10909). It inhibits amyloid fibril formation by amyloidogenic proteins including APP and α-synuclein, facilitates client protein refolding by other chaperones like HSC70, and protects cells against apoptosis and complement-mediated cytolysis by blocking C9 polymerization in the complement membrane attack complex. Intracellular forms interact with ubiquitin-proteasome machinery to degrade target proteins and suppress mitochondrial apoptosis pathways.

Clusterin operates broadly in protein homeostasis and immune regulation. Its diverse roles span extracellular chaperone activity in plasma, intramitochondrial anti-apoptotic signaling, and modulation of neuronal differentiation through STMN3 interaction (UniProt: P10909).

Clusterin shows robust upregulation in Alzheimer's Disease brain tissue, with a mean log2 fold-change of +0.76 in post-mortem AD brain compared to age-matched controls across subcellular fractions (Chaparral AD proteomics). This upregulation is consistent with its established roles in clearing misfolded amyloid species and may reflect a compensatory response to amyloid pathology characteristic of AD.