Beclin-1

Beclin-1 (BECN1) is a core regulatory protein that plays a central role in autophagy, a cellular process essential for protein and organelle degradation (UniProt: Q14457). It functions as a key subunit of the PI3K complex, mediating the formation of phosphatidylinositol 3-phosphate and regulating the initiation and maturation of autophagosomes. Additionally, Beclin-1 is involved in endocytic trafficking, cytokinesis, and may contribute to antiviral host defense mechanisms.

Beclin-1 is widely expressed and its autophagy function is critical across tissues, including the brain where proper protein homeostasis is essential for neuronal health. The protein can also promote apoptosis when localized to mitochondria through BAX translocation and proapoptotic factor release (UniProt: Q14457).

In Alzheimer's Disease, Beclin-1 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: −0.6016, Chaparral AD proteomics). This downregulation suggests impaired autophagy capacity in AD brains, consistent with accumulation of protein aggregates like amyloid-β and tau that characterize the disease pathology. The decreased autophagy flux may contribute to neurodegeneration in Alzheimer's Disease.