S100A10 Protein is a protein. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
Structure
S100A10 (also known as p11) is a small calcium-binding protein belonging to the S100 family. The protein forms a heterotetrameric complex with annexin A2 (ANXA2), which is essential for its biological function. S100A10 lacks calcium-binding ability due to mutations in its EF-hand calcium-binding motifs, but instead serves as a scaffolding protein that recruits annexin A2 to the plasma membrane. The S100A10-ANXA2 complex (also called calpactins) plays crucial roles in membrane organization, endocytosis, and exocytosis.
S100A10 Protein is a protein. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
Structure
S100A10 (also known as p11) is a small calcium-binding protein belonging to the S100 family. The protein forms a heterotetrameric complex with annexin A2 (ANXA2), which is essential for its biological function. S100A10 lacks calcium-binding ability due to mutations in its EF-hand calcium-binding motifs, but instead serves as a scaffolding protein that recruits annexin A2 to the plasma membrane. The S100A10-ANXA2 complex (also called calpactins) plays crucial roles in membrane organization, endocytosis, and exocytosis.
Normal Function in the Nervous System
S100A10[@donato2013] is abundantly expressed in the nervous system with multiple neuronal functions:
Membrane trafficking: The S100A10-ANXA2 complex regulates clathrin-independent endocytosis and exocytosis at the plasma membrane
Synaptic function: Involved in neurotransmitter release through modulation of synaptic vesicle fusion
Cytoskeletal organization: Associates with F-actin and microtubules to regulate cell morphology
Ion channel regulation: Modulates the activity of various ion channels including sodium and calcium channels
Cell migration: Regulates neuronal migration and axonal guidance during development
Role in Neurodegeneration
Alzheimer's Disease
S100A10 is implicated in AD pathogenesis through multiple mechanisms. The protein interacts with the [amyloid precursor protein](/entities/app-protein) (APP) and may influence [amyloid-beta](/proteins/amyloid-beta) production. S100A10 expression is elevated in AD brain, particularly around amyloid plaques, where it may participate in inflammatory responses. Additionally, S100A10 modulates [beta-secretase](/entities/bace1) (BACE1) activity, linking it to amyloidogenesis. Studies show that S100A10 deficiency in mouse models exacerbates cognitive deficits, suggesting a neuroprotective role.
Parkinson's Disease
In PD, S100A10 participates in [alpha-synuclein](/proteins/alpha-synuclein) aggregation and toxicity. The protein can bind to alpha-synuclein and may influence its aggregation kinetics. S100A10[@donato2013] is also involved in microglial activation and neuroinflammation in PD models. The annexin A2 complex regulates dopamine transporter (DAT) trafficking and function, which is relevant to PD pathophysiology.
Amyotrophic Lateral Sclerosis
S100A10 is elevated in ALS and may contribute to disease progression through:
Modulation of [TDP-43](/mechanisms/tdp-43-proteinopathy) aggregation
Regulation of excitatory amino acid transporter (EAAT2) function
Involvement in microglial activation and neuroinflammation
Participation in muscle endplate reorganization
Stroke and Ischemia
S100A10 plays a protective role in cerebral ischemia through:
Anti-apoptotic effects via inhibition of caspase-3
Regulation of [blood-brain barrier](/entities/blood-brain-barrier) integrity
Modulation of inflammatory responses
Therapeutic Targeting
S100A10 is being explored as a therapeutic target for neurodegenerative diseases:
S100A10 inhibitors: Small molecules targeting the S100A10-ANXA2 interaction