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

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.