Investigating the effects of olanzapine on appetite and weight in patients with cancer in a systematic review.

Spinal cord injury (SCI) represents a critical health challenge due to its association with severe disability and mortality (Sutor et al., 2022). SCI encompasses both initial and subsequent injury phases, with the latter being more prolonged and consequential. This phase often leads to oxidative stress, mitochondrial dysfunction, inflammation, and cellular demise (Ni et al., 2022). Emerging research indicates that programmed cell death, incorporating newly identified forms such as necroptosis, autophagy, and pyroptosis, plays a pivotal role in SCI progression (Shi et al., 2021). Consequently, therapeutic strategies targeting cellular death mechanisms are gaining prominence in SCI research. Despite the lack of established clinical treatment protocols for SCI, modulating cell death pathways is increasingly recognized as a promising therapeutic avenue. Traditionally, necrosis was perceived as an unregulated form of cell death. However, recent studies have identified a regulated form of necrosis, referred to as “necroptosis” (Su et al., 2015; Shi et al., 2021). This process, initiated by extracellular signals like TNF-α, involves the formation of a necrosome through assembly of the receptor-interacting protein kinase 1 (RIP)/receptor-interacting protein kinase 3 (RIP3) complex and subsequent phosphorylation of mixed lineage kinase domain-like protein (MLKL). This leads to cellular disruption (Bertheloot et al., 2021). In the context of SCI, necroptosis intensifies the secondary injury, but inhibition of necroptosis has been shown to facilitate spinal cord repair and regeneration post-injury (Fiani et al., 2021). Therefore, targeting necroptosis in neuronal cells has emerged as a promising approach for SCI treatment. In contrast to necroptosis, autophagy (a downregulatory mechanism that is aimed at recycling structural components of the cell) promotes cellular stability. This process helps degrade faulty cellular organelles and harmful byproducts of protein metabolism through the autophagosomal-lysosomal pathway (Shi et al., 2021). Previous research indicates that autophagy impairment in SCI exacerbates neuronal damage and inflammation (Zhang et al., 2023a). Enhancing autophagy in neuronal cells not only aids in the recovery of motor functions but also reduces neuron loss (Li et al., 2022; Zhang et al., 2023b). Due to its role in removing damaged organelles and abnormal proteins, autophagy may be crucial to maintaining neuronal stability and self-renewal after SCI. Moreover, it has been shown that an inverse relationship between autophagy and necroptosis, as promoting autophagy inhibits necroptosis after SCI (Chen et al., 2024). In addition, some necroptosis markers such as MLKL are cleared through the autophagy pathway, and blockade of autophagic flux can inhibit MLKL clearance, thereby exacerbating necroptosis (Liu et al., 2018). Therefore, autophagy acts as a neuroprotective mechanism by modulating neural cell death after SCI. SIRT1, an important member of the sirtuin family, is a Class III histone deacetylase that participates in glucose metabolism, cell survival, mitochondrial respiration regulation, and autophagy (Chen et al., 2022). Members of the mammalian SIRT protein family can interact with p53, FOXO, PGC-1α, NF-κB, Ku70, and other proteins to regulate the cellular stress response, thereby affecting biological processes such as cell metabolism, aging, and apoptosis (Xie et al., 2022). Furthermore, SIRT1 regulates autophagy by deacetylating the autophagy-related genes , , and (Lee et al., 2008). Thus, SIRT1-regulated autophagy may promote SCI repair. SIRT1 has several positive effects on SCI, such as counteracting oxidative stress, reducing cell death, and diminishing disruption of the blood–spinal cord barrier (Yu et al., 2019; Gao et al., 2020; Jiang et al., 2023). Consequently, SIRT1’s neuroprotective properties in the aftermath of SCI have been established, positioning it as a promising therapeutic agent for SCI management.