Neurodegenerative diseases represent a major health threat, with dysfunction in energy metabolism and imbalance in glucose–lipid homeostasis constituting key pathogenic factors. As the cell’s energy hub, mitochondria are closely associated with neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. However, the precise mechanism by which mitochondrial energy metabolism affects glucose–lipid homeostasis remains unclear. This review summarizes currents insights into the role of mitochondrial function in energy metabolism and glucose–lipid regulation in neurodegenerative diseases. We examined how mitochondrial dynamics, oxidative phosphorylation, calcium homeostasis, and key signaling pathways—AMP-activated protein kinase/mammalian target of rapamycin, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, and Sirtuin 1—contribute to neuronal energy balance and metabolic regulation. We further explored the impact of other organelles on mitochondria and how the dynamic switching of mitochondrial morphology and function disrupts the critical glucose–lipid homeostasis. By focusing on mitochondrial dysfunction, metabolic disorders, and their interactions, we introduce the mitochondria-centered multi-organelle–energy metabolic–glucose–lipid homeostasis (MMH) network as a unifying theoretical framework that positions the progressive loss of metabolic flexibility as the fundamental essence of neurodegenerative disorders. The MMH network furnishes a novel lens through which the shared mechanistic underpinnings of neurodegenerative diseases can be deciphered, and thereby enable earlier diagnosis and precision therapeutics.

As an antioxidant, procyanidin B1(PB1) can improve the development of somatic cell nuclear transfer (SCNT) embryos; PB1 reduces the level of oxidative stress (OS) during the in vitro development of SCNT embryos by decreasing the level of reactive oxygen species (ROS) and increasing the level of glutathione (GSH) and mitochondrial membrane potential (MMP). Metabolite hydrogen peroxide (H₂O₂) produces OS. Catalase (CAT) can degrade hydrogen peroxide so that it produces less toxic water (H₂O) and oxygen (O₂) in order to reduce the harm caused by H₂O₂. Therefore, we tested the CAT level in the in vitro development of SCNT embryos; it was found that PB1 can increase the expression of CAT, indicating that PB1 can offset the harm caused by oxidative stress by increasing the level of CAT. Moreover, if H₂O₂ accumulates excessively, it produces radical-(HO-) through Fe^2+/3+ and damage to DNA. The damage caused to the DNA is mainly repaired by the protein encoded by the DNA damage repair gene. Therefore, we tested the expression of the DNA damage repair gene, OGG1. It was found that PB1 can increase the expression of OGG1 and increase the expression of protein. Through the above test, we proved that PB1 can improve the repairability of DNA damage. DNA damage can lead to cell apoptosis; therefore, we also tested the level of apoptosis of blastocysts, and we found that PB1 reduced the level of apoptosis. In summary, our results show that PB1 reduces the accumulation of H₂O₂ by decreasing the level of OS during the in vitro development of SCNT embryos and improves the repairability of DNA damage to reduce cell apoptosis. Our results have important significance for the improvement of the development of SCNT embryos in vitro and provide important reference significance for diseases that can be treated using SCNT technology.

Background: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons, marked by complex pathological mechanisms and a lack of effective treatments. Despite substantial global research efforts, no comprehensive bibliometric analysis has systematically mapped the evolution of ALS biomarkers, therapeutic targets, and pharmacological advancements.Methods: This study, based on 4,250 publications retrieved from the Web of Science Core Collection (2005–2025), employs bibliometric tools such as CiteSpace and VOSviewer to conduct the first multidimensional analysis of global trends in ALS biomarkers, therapeutic targets, and drug research.Results: The results revealed contributions from 20,168 authors across 92 countries, with annual publications growing at an average rate of 16.5%. The United States dominated research output, accounting for 34.07% (n=1,448, TLCS=7,100), while the United Kingdom achieved the highest research impact with an average of 68 citations per article. Leading institutions, including the University of Oxford and the University of Milan, consistently produced high-impact studies. Pioneering scholars such as Turner MR and Kiernan MC made significant contributions to advancing therapeutic targets and drug discovery. The interdisciplinary integration of molecular biology and genetics emerged as a core driver of progress in ALS research. Neurofilament light chain (NfL), antisense oligonucleotide (ASO) drugs, transcranial magnetic stimulation (TMS), oxygen free radicals (oxidative stress), and gene therapy have consistently remained central research focuses in the ALS therapeutic field. Looking ahead, stem cell therapy, blood-brain barrier (BBB) penetration technologies, and skeletal muscle targeting are poised to emerge as prominent research directions.Conclusion: The United States dominates ALS research productivity, whereas the United Kingdom demonstrates superior citation influence. Despite China’s substantial publication volume, its limited citation impact underscores the necessity for enhanced methodological rigor and strategic international collaboration. Current research priorities encompass NfL, TMS, and ASO therapies, with emerging innovations in stem cell therapy, BBB penetration technologies and skeletal muscle targeting showing therapeutic promise. Future directions should prioritize biomarker standardization, optimization of drug delivery systems, and Clinical Translation.

Glioblastoma (GBM) frequently develops resistance to temozolomide (TMZ), a process critically mediated by pro-survival autophagy. While phosphatase signaling plays an essential role in regulating autophagic adaptation, the specific molecular drivers that functionally link phosphatase activity to TMZ resistance through autophagy remain poorly understood. We identified ELFN2 as a brain-enriched PP1 regulatory subunit that inhibits dephosphorylation activity, leading to phosphorylation of the splicing factor SRRM1. This triggers widespread alternative splicing, particularly a proautophagic mutually exclusive exon switch in TMBIM6, thereby promoting autophagy and TMZ resistance. Upstream, the transcription factor LRRC4 represses ELFN2, while the lncRNA LINC00470 sequesters LRRC4 in the cytoplasm to antagonize this repression. Preclinically, the HDAC inhibitor Vorinostat targets ELFN2, restores PP1 activity, and synergizes with TMZ to overcome resistance in vitro and in vivo. Our study reveals a novel PP1-centered phospho-splicing circuit governing pro-survival autophagy in GBM and provides a mechanistically grounded, immediately translatable combination therapy to combat TMZ resistance.