Identification of two distinct synucleins from human brain

TLDR

Two abundant proteins of 140 and 134 amino acids were purified from human brain and identified by immunoblot reactivity with a monoclonal antibody that recognizes tau in a phosphorylation‑dependent manner. The 140‑aa protein is identical to the precursor of the non‑Aβ component of Alzheimer’s amyloid and highly homologous to synuclein, while the 134‑aa protein is the human homologue of bovine phospho‑neuroprotein 14, 61 % identical to the 140‑aa protein, defining a family of human brain synucleins named α‑synuclein and β‑synuclein, both predominantly expressed in presynaptic terminals.

Abstract

Two abundant proteins of 140 and 134 amino acids were purified and sequenced from human brain. They were identified through their reactivity on immunoblots with a partially characterised monoclonal antibody that recognises tau protein in a phosphorylation‐dependent manner. The 140 amino acid protein is identical with the precursor of the non‐Aβ component of Alzheimer's disease amyloid which in turn is highly homologous to synuclein from Torpedo electroplaques and rat brain. The 134 amino acid protein is the human homologue of bovine phosphoneuroprotein 14; it is 61% identical in sequence to the 140 amino acid protein. The previously unrecognised homology between these two proteins defines a family of human brain synucleins. We refer to the 140 and 134 amino acid proteins as α‐synuclein and β‐synuclein, respectively. Both synucleins are expressed predominantly in brain, where they are concentrated in presynaptic nerve terminals.