The p75NTR Signaling Axis: Bridging Neurodevelopmental Homeostasis, Pathological Mechanisms, and Therapeutic Strategies in Neurodegenerative Diseases - PubMed
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- #neurodegenerative diseases
- #therapeutic strategies
- #p75NTR
- The p75NTR receptor plays dual roles in the nervous system, regulated by ligand binding, co-receptor interactions, and microenvironmental cues.
- In neurodegenerative diseases like Alzheimer's, Parkinson's, and ALS, p75NTR activation drives pathological processes such as neuronal apoptosis and axonal degeneration.
- Different structural domains of p75NTR have divergent effects; the extracellular domain (p75ECD) shows neuroprotective properties, while the full-length receptor is pro-apoptotic.
- Therapeutic targeting of p75NTR with small-molecule ligands and ROCK inhibitors has shown efficacy in preclinical models, with some candidates in clinical trials.
- Challenges in clinical translation include unclear mechanisms of p75NTR upregulation, complex downstream signaling, and limited biomarker systems.
- A comprehensive understanding of p75NTR's role in neurodegeneration could reveal new therapeutic targets and clarify pathological mechanisms.