Synergy between amyloid-β and tau in Alzheimer’s disease

Nature Neuroscience, Год журнала: 2020, Номер 23(10), С. 1183 - 1193

Опубликована: Авг. 10, 2020

Язык: Английский

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Biomarkers for neurodegenerative diseases

Nature Medicine, Год журнала: 2021, Номер 27(6), С. 954 - 963

Опубликована: Июнь 1, 2021

Язык: Английский

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Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer’s Disease, Parkinson’s Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis

Chemical Reviews, Год журнала: 2021, Номер 121(4), С. 2545 - 2647

Опубликована: Фев. 5, 2021

Protein misfolding and aggregation is observed in many amyloidogenic diseases affecting either the central nervous system or a variety of peripheral tissues. Structural dynamic characterization all species along pathways from monomers to fibrils challenging by experimental computational means because they involve intrinsically disordered proteins most diseases. Yet understanding how amyloid become toxic challenge developing treatment for these Here we review what computer, vitro, vivo, pharmacological experiments tell us about accumulation deposition oligomers (Aβ, tau), α-synuclein, IAPP, superoxide dismutase 1 proteins, which have been mainstream concept underlying Alzheimer's disease (AD), Parkinson's (PD), type II diabetes (T2D), amyotrophic lateral sclerosis (ALS) research, respectively, years.

Язык: Английский

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The role of TDP-43 propagation in neurodegenerative diseases: integrating insights from clinical and experimental studies

Experimental & Molecular Medicine, Год журнала: 2020, Номер 52(10), С. 1652 - 1662

Опубликована: Окт. 1, 2020

Abstract TAR DNA-binding protein 43 (TDP-43) is a highly conserved nuclear RNA/DNA-binding involved in the regulation of RNA processing. The accumulation TDP-43 aggregates central nervous system common feature many neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease (AD), and limbic predominant age-related encephalopathy (LATE). Accumulating evidence suggests that prion-like spreading aberrant composed tau, amyloid-β, α-synuclein progression diseases AD PD. Similar to those proteins, pathological can be transferred from cell-to-cell seed-dependent self-templating manner. Here, we review clinical experimental studies supporting misfolded discuss molecular mechanisms underlying propagation these aggregated proteins. idea spreads manner between cells may guide novel therapeutic strategies for TDP-43-associated diseases.

Язык: Английский

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The immunology of multiple sclerosis

Nature reviews. Immunology, Год журнала: 2022, Номер 22(12), С. 734 - 750

Опубликована: Май 4, 2022

Язык: Английский

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Genetics and Pathogenesis of Parkinson's Syndrome

Annual Review of Pathology Mechanisms of Disease, Год журнала: 2022, Номер 18(1), С. 95 - 121

Опубликована: Сен. 13, 2022

Parkinson's disease (PD) is clinically, pathologically, and genetically heterogeneous, resisting distillation to a single, cohesive disorder. Instead, each affected individual develops virtually unique form of syndrome. Clinical manifestations consist variable motor nonmotor features, myriad overlaps are recognized with other neurodegenerative conditions. Although most commonly characterized by alpha-synuclein protein pathology throughout the central peripheral nervous systems, distribution varies pathologies modify PD or trigger similar manifestations. Nearly all influenced. More than 100 genes genetic loci have been identified, cases likely arise from interactions among many common rare variants. Despite its complex architecture, insights experimental dissection coalesce reveal unifying biological themes, including synaptic, lysosomal, mitochondrial, andimmune-mediated mechanisms pathogenesis. This emerging understanding syndrome, coupled advances in biomarkers targeted therapies, presages successful precision medicine strategies.

Язык: Английский

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Solving neurodegeneration: common mechanisms and strategies for new treatments

Molecular Neurodegeneration, Год журнала: 2022, Номер 17(1)

Опубликована: Март 21, 2022

Across neurodegenerative diseases, common mechanisms may reveal novel therapeutic targets based on neuronal protection, repair, or regeneration, independent of etiology site disease pathology. To address these and discuss emerging treatments, in April, 2021, Glaucoma Research Foundation, BrightFocus the Melza M. Frank Theodore Barr Foundation collaborated to bring together key opinion leaders experts field for a virtual meeting titled "Solving Neurodegeneration". This "think-tank" style focused uncovering mechanistic roots promising new catalyzed by goal finding treatments glaucoma, world's leading cause irreversible blindness interest three hosting foundations. Glaucoma, which causes vision loss through degeneration optic nerve, likely shares early cellular molecular events with other diseases central nervous system. Here we major areas overlap between system: neuroinflammation, bioenergetics metabolism, genetic contributions, neurovascular interactions. We summarize important discussion points emphasis research that are most innovative treatment neurodegeneration yet require further development. The is highlighted provides unique opportunities collaboration will lead efforts preventing ultimately loss.

Язык: Английский

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The human connectome in Alzheimer disease — relationship to biomarkers and genetics

Nature Reviews Neurology, Год журнала: 2021, Номер 17(9), С. 545 - 563

Опубликована: Июль 20, 2021

Язык: Английский

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Proteomic landscape of Alzheimer’s Disease: novel insights into pathogenesis and biomarker discovery

Molecular Neurodegeneration, Год журнала: 2021, Номер 16(1)

Опубликована: Авг. 12, 2021

Mass spectrometry-based proteomics empowers deep profiling of proteome and protein posttranslational modifications (PTMs) in Alzheimer's disease (AD). Here we review the advances limitations historic recent AD proteomic research. Complementary to genetic mapping, studies not only validate canonical amyloid tau pathways, but also uncover novel components broad networks, such as RNA splicing, development, immunity, membrane transport, lipid metabolism, synaptic function, mitochondrial activity. Meta-analysis seven datasets reveals 2,698 differentially expressed (DE) proteins landscape brain (n = 12,017 proteins/genes), covering 35 reported genes risk loci. The DE contain cellular markers enriched neurons, microglia, astrocytes, oligodendrocytes, epithelial cells, supporting involvement diverse cell types pathology. We discuss hypothesized protective or detrimental roles selected proteins, emphasizing top "amyloidome" (all biomolecules plaques) progression. Comprehensive PTM analysis represents another layer molecular events AD. In particular, PTMs are correlated with stages indicate heterogeneity individual patients. Moreover, unprecedented coverage biofluids, cerebrospinal fluid serum, procures putative biomarkers through meta-analysis. Thus, proteomics-driven systems biology presents a new frontier link genotype, proteotype, phenotype, accelerating development improved models treatment strategies.

Язык: Английский

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The Role of α-Synuclein Oligomers in Parkinson’s Disease

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(22), С. 8645 - 8645

Опубликована: Ноя. 17, 2020

α-synuclein (α-syn) is a protein associated with the pathogenesis of Parkinson's disease (PD), second most common neurodegeneration no effective treatment. However, how α-syn drives pathology PD remains elusive. Recent studies suggest that oligomers are primary cause neurotoxicity and play critical role in PD. In this review, we discuss process formation current understanding structures oligomers. We also describe seed propagation effects oligomeric forms α-syn. Then, summarize mechanism by which exert promote neurodegeneration, including mitochondrial dysfunction, endoplasmic reticulum stress, proteostasis dysregulation, synaptic impairment, cell apoptosis neuroinflammation. Finally, investigate treatment regimens targeting at present. Further research needed to understand structure toxicity different types oligomers, so as provide theoretical basis for

Язык: Английский

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