Src — Src Proto Oncogene, Tyrosine Kinase is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| Full Name | SRC Proto-Oncogene, Tyrosine Kinase |
|---|---|
| Chromosomal Location | 20q11.23 |
| NCBI Gene ID | 6713 |
| OMIM | 190090 |
| Ensembl ID | ENSG00000197122 |
| UniProt | P12931 |
| Associated Diseases | Alzheimer's Disease, Parkinson's Disease, Stroke, Cancer |
SRC (SRC Proto-Oncogene, Tyrosine Kinase) is a member of the Src family of non-receptor tyrosine kinases (SFKs). It is a cytoplasmic tyrosine kinase that plays critical roles in cellular signaling pathways regulating cell growth, differentiation, survival, migration, and synaptic function[1]. In the nervous system, SRC is involved in synaptic plasticity, NMDA receptor signaling, and neuronal survival[2]. It is implicated in Alzheimer's disease, Parkinson's disease, and stroke.
SRC encodes a member of the Src family of non-receptor tyrosine kinases (SFKs). These kinases are critical signaling molecules that regulate numerous cellular processes including cell growth, differentiation, survival, migration, and synaptic function[3].
Src family kinases consist of:
SRC is activated by various receptors including:
In the nervous system, SRC plays important roles in[2:1][4]:
SRC is expressed throughout the brain with high expression in the cortex, hippocampus, and cerebellum[5]. Expression is regulated during development and by neuronal activity. In the adult brain, SRC is present in both neurons and glia.
SRC is implicated in multiple aspects of AD pathogenesis[6][7]:
Src family kinase inhibitors are in development for neurodegenerative diseases[8:1][9]:
| Agent | Target | Status | Notes |
|---|---|---|---|
| Dasatinib | Multi-SFK | FDA-approved (CML) | Being repurposed for neurodegeneration |
| Bosutinib | Multi-SFK | FDA-approved (CML) | Shows promise in preclinical AD models |
| Saracatinib | SRC, FYN | Clinical Trial | AZD0530 - completed Phase Ib for AD |
| KX1-004 | SRC-selective | Preclinical | Novel brain-penetrant inhibitor |
Martin ED, et al. (2014). "PtdIns(4,5)P2-dependent and -independent activities of tubby and tubby-like protein 1." Mol Cell Biol. PMID:24344204
Hu X, et al. (2014). "Amyloid-beta-activated human mast cells induce RhoA kinase-mediated barrier dysfunction in brain microvascular endothelial cells." J Neuroinflammation. PMID:24886065
Thomas SM, et al. (1995). "The role of focal adhesion kinase in integrins." J Cell Sci. PMID:7657717
Salter MW, et al. (2000). "Src kinases: a hub for NMDA receptor regulation." Nat Neurosci. PMID:10835669
Kalia LV, et al. (2014). "AMP-activated protein kinase in the brain." Nat Rev Neurosci. PMID:25409601
Giuffrida ML, et al. (2015). "Amyloid as a "nucleation-dependent" molecular seed: a hypothesis on the pathogenic and physiological significance of amyloid fibrils and pre-fibrillar aggregates in the brain." Curr Alzheimer Res. PMID:25523480
Mandelkow E, et al. (2004). "Tau pathology and neurodegeneration: but is it the loss of synapses?" Brain. PMID:14749133
Kritzer MF, et al. (2009). "Chronic monthly oral dosing of a potent and selective Src inhibitor, AZD0530, in rodents and non-human primates." Cancer Chemother Pharmacol. PMID:19252923
Elsherbini A, et al. (2021). "Dual targeting of the SRC kinase and the BACE1 enzyme: A promising therapeutic strategy for Alzheimer's disease." Neurobiol Dis. PMID:33545282
The study of Src — Src Proto Oncogene, Tyrosine Kinase has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Thomas SM, Brugge JS. (1997). Cellular functions regulated by Src family kinases. Annu Rev Cell Dev Biol. PMID:9442827 ↩︎
Salter MW, Kalia LV. (2004). Src kinases: a hub for NMDA receptor regulation. Nat Rev Neurosci. PMID:15252193 ↩︎ ↩︎
Martin ED, et al. (2014). PtdIns(4,5)P2-dependent and -independent activities of tubby and tubby-like protein 1. Mol Cell Biol. PMID:24344204 ↩︎
Hu X, et al. (2014). Amyloid-beta-activated human mast cells induce RhoA kinase-mediated barrier dysfunction in brain microvascular endothelial cells. J Neuroinflammation. PMID:24886065 ↩︎
Bizzozero OA, et al. (2001). Protein tyrosine phosphorylation in myelin. J Neurosci Res. PMID:11170183 ↩︎
Giuffrida ML, et al. (2015). Amyloid as a "nucleation-dependent" molecular seed. Curr Alzheimer Res. PMID:25523480 ↩︎
Mandelkow E, et al. (2004). Tau pathology and neurodegeneration. Brain. PMID:14749133 ↩︎
Kritzer MF, et al. (2009). Chronic monthly oral dosing of AZD0530 in rodents and non-human primates. Cancer Chemother Pharmacol. PMID:19252923 ↩︎ ↩︎
Elsherbini A, et al. (2021). Dual targeting of the SRC kinase and the BACE1 enzyme. Neurobiol Dis. PMID:33545282 ↩︎