Mechanisms of treatment of neurodegenerative diseases (NDs) using capsaicin and N-oleoyldopamin (OLDA)

Potential mechanisms of treatment of neurodegenerative diseases (NDs) using capsaicin and N-oleoyldopamin (OLDA). (a) Capsaicin activates the TRPV1 receptor and Ca2+ influx, which can induce the upregulation of microglia phagocytosis, regulate its metabolic process and inhibit oxidative stress in microglia and astrocytes. It also can mediate the endogenous production of ciliary neurotrophic factor (CNTF), thereby stimulating activity of tyrosine hydroxylase (TH) enzyme and activating endogenous neuroprotective mechanisms. Activation of the TRPV1 channel upregulates the AKT/mTOR signaling pathway and reduces the production of inflammatory molecules. (b) OLDA in the human body comes from two pathways: one is the combination of dopamine and oleic acid under the action of fatty acid amide hydrolase (FAAH). Moreover, clostridium in the intestine can also bind foreign substrates (fatty acids) commonly found in the human body or diet with amines under the action of non-ribosomal peptide synthases (NRPS) to produce OLDA. OLDA can reach the brain via the blood–brain barrier (BBB), enhancing thermal and mechanical hypersensitivity by activating the TRPV1 receptor. OLDA activates TRPV1 and blocking dopamine transporter (DAT) and dopamine 2 receptor (D2R) activation, and then leads to a wake-on-firing pattern of histaminergic (HA) neurons, which may have beneficial effects on the treatment of PD

Publication

Impact of TRPV1 on Pathogenesis and Therapy of Neurodegenerative Diseases (2024) Wenxin Wang, et al. Molecules. 2024 Jan;29(1). Figure: F4. Homo sapiens

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