Ntrk1 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
:: infobox .infobox-gene
Symbol: NTRK1
Full Name: Neurotrophic Receptor Tyrosine Kinase 1
Chromosomal Location: 1q23.1
NCBI Gene ID: 4914
OMIM: 191315
Ensembl ID: ENSG00000159479
UniProt: P04629
Proteins: TrkA
Associated Diseases: Congenital Insensitivity to Pain with Anhidrosis (CIPA), Alzheimer's Disease
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NTKR1 is a gene/protein encoding a key neuronal protein involved in synaptic function, signal transduction, and cellular homeostasis. Dysfunction of NTKR1 is associated with neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and related disorders.
NTRK1 encodes TrkA (Tropomyosin receptor kinase A), the primary receptor for nerve growth factor (NGF). TrkA is a receptor tyrosine kinase that plays critical roles in neuronal development, survival, and function. In the adult nervous system, TrkA signaling promotes the survival of specific neuronal populations including nociceptors, thermoreceptors, and cholinergic neurons in the basal forebrain. In Alzheimer's disease, NGF/TrkA signaling is impaired, and restoring this pathway has been explored as a therapeutic strategy.
TrkA is expressed in:
- Basal forebrain cholinergic neurons
- Dorsal root ganglia (sensory neurons)
- Sympathetic neurons
- Hippocampus (subtle expression)
- Cortex (layer 5 pyramidal neurons)
High expression in regions undergoing neurodegeneration in AD makes it a therapeutic target.
- Hempstead BL, et al. (1991). "TrkA: a receptor for nerve growth factor." Cold Spring Harb Symp Quant Biol. PMID:1669073
- Chao MV, et al. (2006). "Neurotrophins: roles in neuronal development and function." Annu Rev Neurosci. PMID:16719985
- Longo FM, et al. (2013). "Small molecule neurotrophin receptor agonists for Alzheimer's disease." J Alzheimers Dis. PMID:23948871
The study of Ntrk1 Gene 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.
- Doebele RC et al.. "Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials." The Lancet. Oncology (2020). DOI: 10.1016/S1470-2045(19)30691-6 PubMed: 31838007
- Obeidat AM et al.. "Piezo2 expressing nociceptors mediate mechanical sensitization in experimental osteoarthritis." Nature communications (2023). DOI: 10.1038/s41467-023-38241-x PubMed: 37120427
- Jiang T et al.. "Development of small-molecule tropomyosin receptor kinase (TRK) inhibitors for NTRK fusion cancers." Acta pharmaceutica Sinica. B (2021). DOI: 10.1016/j.apsb.2020.05.004 PubMed: 33643817
- Gianno F et al.. "Paediatric-type diffuse high-grade gliomas in the 5th CNS WHO Classification." Pathologica (2022). DOI: 10.32074/1591-951X-830 PubMed: 36534421
- Megarbane A et al.. "A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort." Journal of neuromuscular diseases (2022). DOI: 10.3233/JND-210652 PubMed: 34602496
- Clarke M et al.. "Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes." Cancer discovery (2020). DOI: 10.1158/2159-8290.CD-19-1030 PubMed: 32238360
- Yang K et al.. "NTRK1 knockdown induces mouse cognitive impairment and hippocampal neuronal damage through mitophagy suppression via inactivating the AMPK/ULK1/FUNDC1 pathway." Cell death discovery (2023). DOI: 10.1038/s41420-023-01685-7 PubMed: 37907480
- Bogumil H et al.. "Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA): a molecularly distinct brain tumor type with recurrent NTRK gene fusions." Acta neuropathologica (2023). DOI: 10.1007/s00401-023-02558-0 PubMed: 36933012