Unraveling the mechanistic interplay of mediators orchestrating the neuroprotective potential of harmine.

AChE BDNF DYRK1A GLT-1 Harmine Neuroprotection α-synuclein

Journal

Pharmacological reports : PR

ISSN: 2299-5684

Titre abrégé: Pharmacol Rep

Pays: Switzerland

ID NLM: 101234999

Informations de publication

Date de publication:
17 May 2024

Historique:

received: 18 02 2024

accepted: 07 05 2024

revised: 27 04 2024

medline: 17 5 2024

pubmed: 17 5 2024

entrez: 17 5 2024

Statut: aheadofprint

Résumé

Neurodegenerative diseases (NDDs) encompass a range of conditions characterized by the specific dysfunction and continual decline of neurons, glial cells, and neural networks within the brain and spinal cord. The majority of NDDs exhibit similar underlying causes, including oxidative stress, neuroinflammation, and malfunctioning of mitochondria. Elevated levels of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), alongside decreased expression of brain-derived neurotrophic factor (BDNF) and glutamate transporter subtype 1 (GLT-1), constitute significant factors contributing to the pathogenesis of NDDs. Additionally, the dual-specificity tyrosine phosphorylation-regulated kinase 1 A (DYRK1A) gene has emerged as a significant target for the treatment of NDDs at the preclinical level. It significantly contributes to developmental brain defects, early onset neurodegeneration, neuronal loss, and dementia in Down syndrome. Moreover, an impaired ubiquitin-proteosome system (UPS) also plays a pathological role in NDDs. Malfunctioning of UPS leads to abnormal protein buildup or aggregation of α-synuclein. α-Synuclein is a highly soluble unfolded protein that accumulates in Lewy bodies and Lewy neurites in Parkinson's disease and other synucleinopathies. Recent research highlights the promising potential of natural products in combating NDDs relative to conventional therapies. Alkaloids have emerged as promising candidates in the fight against NDDs. Harmine is a tricyclic β-carboline alkaloid (harmala alkaloid) with one indole nucleus and a six-membered pyrrole ring. It is extracted from Banisteria caapi and Peganum harmala L. and exhibits diverse pharmacological properties, encompassing neuroprotective, antioxidant, anti-inflammatory, antidepressant, etc. Harmine has been reported to mediate its neuroprotective via reducing the level of inflammatory mediators, NADPH oxidase, AChE, BChE and reactive oxygen species (ROS). Whereas, it has been observed to increase the levels of BDNF, GLT-1 and anti-oxidant enzymes, along with protein kinase-A (PKA)-mediated UPS activation. This review aims to discuss the mechanistic interplay of various mediators involved in the neuroprotective effect of harmine.

Identifiants

DOI: 10.1007/s43440-024-00602-8 PMID: 38758470

pubmed: 38758470

doi: 10.1007/s43440-024-00602-8

pii: 10.1007/s43440-024-00602-8

doi:

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

Informations de copyright

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