Research on the molecular mechanism of singularity phenomenon in neurological disordersстатья из журнала
Аннотация: In Alzheimer's disease (AD), toxic oligomers of tau proteins originate from a small number of cells deep inside the brain and propagate to other regions of the brain, ultimately causing cell death in up to 50% of neurons in the cerebral cortex.Based on the pathological observations of over 2000 brains [1,2], it has been hypothesized that the phosphorylated tau, the primary cause of tauopathy, initially appears in the locus coeruleus (LC) in the brainstem and entorhinal cortex (EC), spreading from there to the hippocampus and cerebral cortex.Integrating results from these human pathological anatomy and animal experiments [3] suggests that tau aggregation begins in a small number of neurons in LC and/or EC, and rapidly expands to affect the entire brain at some point.This phenomenon is considered a "singularity phenomenon", and neurons in LC and EC that acquired an ability to propagate toxic tau are referred to as "singularity cells".Interestingly, the formation of protein aggregates and their propagation from one brain region to another are common pathogenesis mechanisms shared by various neurodegenerative diseases.Amyloid β (Aβ), α-synuclein, and TAR DNA-binding protein 43 (TDP-43), which are found as aggregates in the patients of AD, Parkinson's disease as well as dementia with Lewy bodies, and amyotrophic lateral sclerosis (ALS), respectively, are also characterized by the expansion of large-scale neurodegeneration starting from a few cells [4].These neurodegenerative diseases can also be considered "singularity phenomena".However, traditional research has not viewed neurodegenerative diseases as having a "singularity", or the cells forming toxic protein aggregates and gaining the ability to propagate aggregates have not been recognized as "singularity cells" in the onset of neurodegenerative diseases.To understand the mechanisms underlying these neuronal diseases and to advance prevention and treatment, it is essential to seamlessly analyze the process of accumulation of aggregated proteins, which gives rise to singularity cells and causes damage to neurons and the entire brain, across molecular, cellular, and tissue levels.
Год издания: 2024
Авторы: Hiroko Bannai, Akihiko Takashima, Yoshiyuki Soeda, Hideaki� Yoshimura, Gen Matsumoto, Naruhiko Sahara, Michio Hiroshima, Mitsuru Hattori, Takeharu Nagai
Издательство: Biophysical Society of Japan
Источник: Biophysics and Physicobiology
Ключевые слова: Alzheimer's disease research and treatments, Prion Diseases and Protein Misfolding, Cholinesterase and Neurodegenerative Diseases
Другие ссылки: Biophysics and Physicobiology (PDF)
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PubMed Central (HTML)
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Biophysics and Physicobiology (HTML)
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Том: 21
Выпуск: Supplemental
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