Identification of two distinct synucleins from human brain

Area of Science:

• Neuroscience
• Molecular Biology
• Biochemistry

Background:

• Two abundant proteins, 140 and 134 amino acids long, were purified and sequenced from human brain tissue.
• Identification was achieved using immunoblots with a monoclonal antibody recognizing tau protein in a phosphorylation-dependent manner.

Purpose of the Study:

• To identify and characterize two abundant, novel proteins from human brain.
• To investigate the relationship and homology between these proteins and known synucleins.

Main Methods:

• Protein purification and sequencing from human brain.
• Immunoblot analysis using a phosphorylation-dependent anti-tau monoclonal antibody.
• Sequence homology comparison with known synuclein proteins and bovine phosphoneuroprotein 14.

Main Results:

• The 140 amino acid protein is identical to the precursor of non-A beta component of Alzheimer's disease amyloid, homologous to synuclein.
• The 134 amino acid protein is the human homologue of bovine phosphoneuroprotein 14, sharing 61% sequence identity with the 140 amino acid protein.
• A previously unrecognized homology was found, defining a family of human brain synucleins: alpha-synuclein (140 aa) and beta-synuclein (134 aa).

Conclusions:

• Two distinct human brain synucleins, alpha-synuclein and beta-synuclein, have been identified and characterized.
• These proteins are predominantly expressed in the brain and concentrated in presynaptic nerve terminals.
• The discovery establishes a new family of synuclein proteins in the human brain.