Isoform 3 of Drebrin

Drebrin (DBN1) is an actin-binding protein that regulates cytoskeletal dynamics and dendritic spine morphology through its interactions with actin filaments (UniProt: Q16643-3). The protein is primarily expressed in neuronal tissue, where it plays a crucial role in synaptic plasticity and neuronal architecture. Its function in stabilizing and organizing actin structures is essential for maintaining synaptic integrity and dendritic function.

Isoform 3 of Drebrin is significantly associated with Alzheimer's Disease pathology. In post-mortem AD brain tissue compared to age-matched controls, this protein is consistently downregulated across subcellular fractions, with a mean log2 fold-change of −0.73 (Chaparral AD proteomics). The experiment employed TMT-labeled tandem mass spectrometry across four subcellular compartments (P2, P3, S2, S3), demonstrating robust evidence of reduced Drebrin expression in AD.

The downregulation of Drebrin in AD suggests impaired cytoskeletal dynamics and compromised synaptic structural integrity, consistent with synaptic loss observed in Alzheimer's pathology. Loss of this actin-regulatory protein may contribute to dendritic spine deterioration and cognitive decline characteristic of the disease.