TrkA - Histology

What is TrkA?

TrkA, also known as tropomyosin receptor kinase A, is a high-affinity receptor for nerve growth factor (NGF). It belongs to the Trk family of receptor tyrosine kinases, which are critical for the development and function of the nervous system. TrkA signaling plays a fundamental role in the differentiation, survival, and maintenance of specific neuronal populations.

Where is TrkA Expressed?

TrkA is predominantly expressed in sensory neurons and sympathetic neurons of the peripheral nervous system. It is also found in certain regions of the central nervous system, particularly those involved in pain and temperature sensation. Outside the nervous system, TrkA expression is observed in tissues such as the immune system and epithelial cells.

How Does TrkA Function?

Upon binding to NGF, TrkA undergoes dimerization and autophosphorylation on specific tyrosine residues. This activation triggers multiple downstream signaling pathways such as the PI3K/Akt pathway, the Ras/MAPK pathway, and the PLCγ pathway. These pathways collectively promote cell survival, growth, and differentiation.

What are the Histological Techniques to Study TrkA?

Several histological techniques are employed to study TrkA expression and function. Immunohistochemistry (IHC) is commonly used to visualize TrkA in tissue sections by using specific anti-TrkA antibodies. Western blotting and ELISA are also utilized to quantify TrkA levels. Additionally, in situ hybridization can be performed to detect TrkA mRNA in tissues.

What is the Role of TrkA in Disease?

Alterations in TrkA signaling are implicated in various diseases. For instance, mutations in the TrkA gene can cause congenital insensitivity to pain with anhidrosis (CIPA), a rare genetic disorder. Overexpression of TrkA has been linked to certain types of cancers, such as neuroblastoma. Conversely, reduced TrkA activity is associated with neurodegenerative diseases like Alzheimer's disease.

How is TrkA Targeted Therapeutically?

Given its critical role in neuronal survival and disease, TrkA has become a therapeutic target. NGF mimetics and TrkA agonists are being developed to treat neurodegenerative diseases by enhancing TrkA signaling. Conversely, TrkA inhibitors are being explored for the treatment of cancers where TrkA is aberrantly activated.

Relevant Publications

Dual inhibition of the TrkA and JAK2 pathways using entrectinib and pacritinib suppresses the growth and metastasis of HER2-positive and triple-negative breast cancers.

Issue Release: 2024

Zurletrectinib is a next-generation TRK inhibitor with strong intracranial activity against NTRK fusion-positive tumours with on-target resistance to first-generation agents.

Issue Release: 2024

Pyrazolo[1,5-]pyrimidine as a Prominent Framework for Tropomyosin Receptor Kinase (Trk) Inhibitors-Synthetic Strategies and SAR Insights.

Issue Release: 2024

Modulation of the p75NTR during Adolescent Alcohol Exposure Prevents Cholinergic Neuronal Atrophy and Associated Acetylcholine Activity and Behavioral Dysfunction.

Issue Release: 2024

Retraction: PKCδ null mutations in a mouse model of osteoarthritis alter osteoarthritic pain independently of joint pathology by augmenting NGF/TrkA-induced axonal outgrowth.

Issue Release: 2024

Metformin inhibits nerve growth factor (NGF)-induced sympathetic neuron differentiation through p35/CDK5 inhibition.

Issue Release: 2024

Discovery of 9H-pyrimido[4,5-b]indole derivatives as dual RET/TRKA inhibitors.

Issue Release: 2024

Nigrostriatal inflammation is associated with nonmotor symptoms in an experimental model of prodromal Parkinson\'s disease.

Issue Release: 2024

Genetic etiology study in a large cohort with congenital insensitivity to pain with anhidrosis.

Issue Release: 2024

NTRK2 expression in gastrointestinal stromal tumors with a special emphasis on the clinicopathological and prognostic impacts.

Issue Release: 2024

NGF contributes to activities of acid-sensing ion channels in dorsal root ganglion neurons of male rats with experimental peripheral artery disease.

Issue Release: 2024

Docking protein 6 (DOK6) selectively docks the neurotrophic signaling transduction to restrain peripheral neuropathy.

Issue Release: 2024

Regulation of metabolism and proton motive force generation during mixed carbon fermentation by an Escherichia coli strain lacking the FF-ATPase.

Issue Release: 2024

Primary NTRK-rearranged Spindle Cell Neoplasm of the Gastrointestinal Tract: A Clinicopathological and Molecular Analysis of 8 Cases.

Issue Release: 2024

A Study of Alternative TrkA Splicing Identifies TrkAIII as a Novel Potentially Targetable Participant in PitNET Progression.

Issue Release: 2024

Neuroprotection of Cholinergic Neurons with a Tau Aggregation Inhibitor and Rivastigmine in an Alzheimer\'s-like Tauopathy Mouse Model.

Issue Release: 2024

The expression system affects the binding affinity between p75NTR and proNGF.

Issue Release: 2024

Suppression of CGRP and TRPV1 Expression in Dorsal Root Ganglia of Knee Osteoarthritis Rats by Huojing Decoction via TrkA/MKK3/6/p38 Pathway.

Issue Release: 2024

A structured biomimetic nanoparticle as inflammatory factor sponge and autophagy-regulatory agent against intervertebral disc degeneration and discogenic pain.

Issue Release: 2024

Physical Stimulation Methods Developed for In Vitro Neuronal Differentiation Studies of PC12 Cells: A Comprehensive Review.

Issue Release: 2024

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