Neurodegenerative diseases (NDs) are a group of neurological disorders characterized by the progressive dysfunction of neurons and glial cells, leading to their structural and functional degradation in the central and/or peripheral nervous system. Historically, research on NDs has primarily focused on the brain, brain stem, or spinal cord associated with disease-related symptoms, often overlooking the role of the cerebellum. However, an increasing body of clinical and biological evidence suggests a significant connection between the cerebellum and NDs. In several NDs, cerebellar pathology and biochemical changes may start in the early disease stages. This article provides a comprehensive update on the involvement of the cerebellum in the clinical features and pathogenesis of multiple NDs, suggesting that the cerebellum is involved in the onset and progression of NDs through various mechanisms, including specific neurodegeneration, neuroinflammation, abnormal mitochondrial function, and altered metabolism. Additionally, this review highlights the significant therapeutic potential of cerebellum-related treatments for NDs.
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http://dx.doi.org/10.1016/j.isci.2024.111194 | DOI Listing |
Alzheimers Res Ther
January 2025
Department of Neuroscience "Rita Levi Montalcini", University of Turin, Via Cherasco 15, Turin, 10126, Italy.
Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with both genetic and environmental factors contributing to its pathogenesis. While early-onset AD has well-established genetic determinants, the genetic basis for late-onset AD remains less clear. This study investigates a large Italian family with late-onset autosomal dominant AD, identifying a novel rare missense variant in GRIN2C gene associated with the disease, and evaluates the functional impact of this variant.
View Article and Find Full Text PDFBiol Res
January 2025
School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, China.
Background: Protein palmitoylation, a critical posttranslational modification, plays an indispensable role in various cellular processes, including the regulation of protein stability, mediation of membrane fusion, facilitation of intracellular protein trafficking, and participation in cellular signaling pathways. It is also implicated in the pathogenesis of diseases, such as cancer, neurological disorders, inflammation, metabolic disorders, infections, and neurodegenerative diseases. However, its regulatory effects on sperm physiology, particularly motility, remain unclear.
View Article and Find Full Text PDFMol Brain
January 2025
Graduate Program in Neuroscience, University of Washington, Seattle, WA, 98195, USA.
Recent research has highlighted widespread dysregulation of alternative polyadenylation in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). Here, we identify significant disruptions to 3` UTR polyadenylation in the ALS/FTLD-TDP mouse model rNLS8 that correlate with changes in gene expression and protein levels through the re-analysis of published RNA sequencing and proteomic data. A subset of these changes are shared with TDP-43 knock-down mice suggesting depletion of endogenous mouse TDP-43 is a contributor to polyadenylation dysfunction in rNLS8 mice.
View Article and Find Full Text PDFBMC Med Genomics
January 2025
Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK.
Amyotrophic lateral sclerosis (ALS) lacks a specific biomarker, but is defined by relatively selective toxicity to motor neurons (MN). As others have highlighted, this offers an opportunity to develop a sensitive and specific biomarker based on detection of DNA released from dying MN within accessible biofluids. Here we have performed whole genome bisulfite sequencing (WGBS) of iPSC-derived MN from neurologically normal individuals.
View Article and Find Full Text PDFCommun Biol
January 2025
Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX, USA.
Aggregation of microtubule-associated tau protein is a distinct hallmark of several neurodegenerative disorders such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and progressive supranuclear palsy (PSP). Tau oligomers are suggested to be the primary neurotoxic species that initiate aggregation and propagate prion-like structures. Furthermore, different diseases are shown to have distinct structural characteristics of aggregated tau, denoted as polymorphs.
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