Editorial: Biomarkers and therapeutic targets in the pathogenesis of neurodegenerative diseases: Functions, implications, and perspectives

RNAs etc.) in NDs and their potentials as disgnostic biomarkers and therapeutic targets in these diseases.Adult Degenerative Scoliosis (ADS) is a debilitating spine condition with asymmetric spinal degeneration and multiaxial rotational deformity due to progressive degenerative changes (Philip et al., 2017). A research article from Shi et al. deployed whole-transcriptome sequencing to explore the difference between common disc degeneration and ADS, which could indicate the potential mechanism of ADS. In their study, varieties of RNA, including circRNA, long noncoding RNAs (lncRNA), miRNA, and mRNA expression profiles were investigated.Differentially expressed (DE) RNAs were conspicuously identified in ADS group compared to their counterparts in disc herniation group: 3322 DE mRNAs,221 DE lncRNAs,20 DE miRNAs,and 15 DE circRNAs in the ADS. Among RNAs, most of them were relevant with the biological function of endocytosis, apoptosis, etc. Therefore, this study provided the evidences supporting potential role of non-coding RNAs in ADS aetiology.He et al. summarized the recent progress of research on exploring the roles of non-coding RNAs in NDs (AD, PD, TBI, etc.) by especially focusing on circular RNAs (circRNAs). With a closed circular structure, CircRNAs are more stable in cells than their liner mRNA counterparts, and becoming very promising candidates for gene therapy (Wu et al., 2022). The review discussed the sponge function of circRNAs, emphasized the fact that individual circRNA could sponge different miRNAs and actively interacted with other mRNAs and noncoding RNAs and postulated a possible circRNA-miRNA-mRNA network which could be part of complicated regulation system during the development of NDs.Noncoding RNAs could also function as potential messengers between neurons and glial cells and circulate in the body fluids for communication since of their ability to cross the blood-brain barrier. Wang et al. has another review article delineated the exosomal noncoding RNAs including miRNAs, lncRNAs, circRNAs, and PIWI-interacting RNAs (piRNAs) about their role in Central Nervous System (CNS) diseases, especially NDs (AD, PD, etc.). Exosomes in the niches of CNS have crucial impacts on the interplay between cells (neuron-neuron, neuron-glia, etc.) by carrying small molecules, including RNAs. This review summarized the recent research progress of the exosomal noncoding RNAs in CNS disorders and discussed the potentials of the small molecules containing exosomes as diagnostic biomarkers and therapeutic applications.Fluid biomarkers (soluble amyloid, tau and α-synuclein, etc.) have been the hot topics in the decade for the research of NDs with the hope of finding diagnostic markers. Further understanding of exosomal noncoding RNAs will certainly make these molecules to be potential candidates in this field.Autophagy is the major intracellular mechanism for degrading accumulated misfolded proteins.The defect of autophagy pathways has been proved be closely associated with NDs at different stages (Fang et al., 2018). Basri et al. provided another literature review updating the recent research on how circRNAs participated in the regulation mechanism of NDs to make the autophagy cascade being orchestrated in a systemic way. The idea derived from the facts that circRNAs tendes to accumulate in the aging CNS and aging is the major predisposing factor of NDs. The interplay between circRNAs, autophagy and varieties of NDs (AD, PD, ALS, HD and SMA, ect.) was profiled in this review according to the recent publications.In another report with the proteome and transcriptome studies of ischemia, He et al. used hippocampal neuronal HT22 cell line to study NMDA receptor (NMDAR) mediated excitotoxicity and NMDAR hypofunction via a ischemic insult model or deleting the receptor.NMDA receptor has complex role in cerebral ischemia by exerting both pro-death and prosurvival signaling pathways (Li et al., 2022). The data presented here was aimed to depict the proteome and transcriptome profiles among "hyper" and "hypo" NMDA receptors. Interesting expression patterns of protein and RNA in these two groups were identified, which could provide indication for future study of the dynamic change of NMDA receptor during ischemic insult.Transplantation of neuronal stem cells in NDs has shown promising results and the stem cellbased therapy against NDs is the hot topic in the current therapeutic area of NDs (Singh et al., 2016). A research article from Gupta et al. found imidazole-based GSK-3β inhibitors could facilate the transdifferentiation of human mesenchymal stem cells (MSC) to neurons, which provided a novel platform with a potential single-molecule formula instead of a "chemical cocktail" solution to induce the transdifferentiation.Cerebral small vessel disease (CSVD) is considered as the most common etiology of vascular dementia or cognitive dysfunction and contributes to the pathogenesis of AD (Hae et al., 2020).Zou et al. performed the gene differential analysis of AD and CSVD patients from public databases to explore the underlying molecular mechanisms associated with both diseases.Differentially expressed genes (DEGs) were identified and most of DEGs were linked to endocytosis and oxytocin signaling pathways. Among the DEGs, SIRT1, a obesity and metabolic related gene was postulated as a key gene. These results were reasonable since aberrant lipid metabolism is strong risk for AD. Take together, this Research Topic mostly highlights the novel mechanism of NDs by focusing multiple types of RNAs, especially noncoding RNA and circular RNAs. The collected articles here will add significant value on further understanding of NDs via novel perspectives.

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