Targeting apoptosis and autophagy following spinal cord injury: Therapeutic approaches to polyphenols and candidate phytochemicals

Abbaszadeh, F. and Fakhri, S. and Khan, H. (2020) Targeting apoptosis and autophagy following spinal cord injury: Therapeutic approaches to polyphenols and candidate phytochemicals. Pharmacological Research, 160.

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Abstract

Spinal cord injury (SCI) is a neurological disorder associated with the loss of sensory and motor function. Understanding the precise dysregulated signaling pathways, especially apoptosis and autophagy following SCI, is of vital importance in developing innovative therapeutic targets and treatments. The present study lies in the fact that it reveals the precise dysregulated signaling mediators of apoptotic and autophagic pathways following SCI and also examines the effects of polyphenols and other candidate phytochemicals. It provides new insights to develop new treatments for post-SCI complications. Accordingly, a comprehensive review was conducted using electronic databases including, Scopus, Web of Science, PubMed, and Medline, along with the authors� expertise in apoptosis and autophagy as well as their knowledge about the effects of polyphenols and other phytochemicals on SCI pathogenesis. The primary mechanical injury to spinal cord is followed by a secondary cascade of apoptosis and autophagy that play critical roles during SCI. In terms of pharmacological mechanisms, caspases, Bax/Bcl-2, TNF-α, and JAK/STAT in apoptosis along with LC3 and Beclin-1 in autophagy have shown a close interconnection with the inflammatory pathways mainly glutamatergic, PI3K/Akt/mTOR, ERK/MAPK, and other cross-linked mediators. Besides, apoptotic pathways have been shown to regulate autophagy mediators and vice versa. Prevailing evidence has highlighted the importance of modulating these signaling mediators/pathways by polyphenols and other candidate phytochemicals post-SCI. The present review provides dysregulated signaling mediators and therapeutic targets of apoptotic and autophagic pathways following SCI, focusing on the modulatory effects of polyphenols and other potential phytochemical candidates. © 2020 Elsevier Ltd

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: apocynin; beclin 1; butein; calcium ion; calpain 1; caspase 3; caspase 9; curcumin; cytochrome c; Fas ligand; heat shock protein; inducible nitric oxide synthase; interleukin 1beta converting enzyme; Janus kinase 1; mitochondrial permeability transition pore; nicotinamide adenine dinucleotide; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1; phospholipase; piceid; polyphenol; procaspase 8; protein Bax; protein bcl 2; resveratrol; STAT protein; stress activated protein kinase 1; tumor necrosis factor; tumor necrosis factor receptor associated death domain protein; tumor necrosis factor receptor associated factor 1; unindexed drug, apoptosis; astrocyte; autophagosome; autophagy (cellular); calcium transport; cell damage; cell survival; DNA fragmentation; drug approval; drug efficacy; drug mechanism; drug response; drug structure; human; membrane permeability; mitochondrial membrane; nerve cell; neuroprotection; oxidative phosphorylation; phytochemistry; presynaptic nerve; priority journal; protein binding; protein cleavage; protein expression; protein phosphorylation; protein secretion; Review; spinal cord injury; systematic review; tissue injury; upregulation
Subjects: WL Nervous System
Depositing User: eprints admin
Date Deposited: 03 Oct 2020 06:41
Last Modified: 03 Oct 2020 06:41
URI: http://eprints.iums.ac.ir/id/eprint/23034

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