Hallmarks of neurodegenerative diseases

Cell, Journal Year: 2023, Volume and Issue: 186(4), P. 693 - 714

Published: Feb. 1, 2023

Summary

Decades of research have identified genetic factors and biochemical pathways involved in neurodegenerative diseases (NDDs). We present evidence for the following eight hallmarks NDD: pathological protein aggregation, synaptic neuronal network dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, DNA RNA defects, inflammation, cell death. describe hallmarks, their biomarkers, interactions as a framework to study NDDs using holistic approach. The can serve basis defining pathogenic mechanisms, categorizing different based on primary stratifying patients within specific NDD, designing multi-targeted, personalized therapies effectively halt NDDs.

Language: Английский

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Liquid–Liquid Phase Separation in Disease

Annual Review of Genetics, Journal Year: 2019, Volume and Issue: 53(1), P. 171 - 194

Published: Aug. 20, 2019

We have made rapid progress in recent years identifying the genetic causes of many human diseases. However, despite this progress, our mechanistic understanding these diseases is often incomplete. This a problem because it limits ability to develop effective disease treatments. To overcome limitation, we need new concepts describe and comprehend complex mechanisms underlying Condensate formation by phase separation emerges as principle explain organization living cells. In review, present emerging evidence that aberrant forms condensates are associated with diseases, including cancer, neurodegeneration, infectious examine driven condensates, point out opportunities for therapeutic interventions. conclude provides useful framework understand fight some most severe

Language: Английский

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Nanocatalytic Medicine

Advanced Materials, Journal Year: 2019, Volume and Issue: 31(39)

Published: July 22, 2019

Abstract Catalysis and medicine are often considered as two independent research fields with their own respective scientific phenomena. Promoted by recent advances in nanochemistry, large numbers of nanocatalysts, such nanozymes, photocatalysts, electrocatalysts, have been applied vivo to initiate catalytic reactions modulate biological microenvironments for generating therapeutic effects. The rapid growth biomedical applications nanocatalysts has led the concept “nanocatalytic medicine,” which is expected promote further advance a subdiscipline nanomedicine. high efficiency selectivity catalysis that chemists strived achieve past century can be ingeniously translated into efficacy mitigated side effects theranostics using medicine” steer optimized outcomes. Here, rationale behind construction nanocatalytic eludicated based on essential reaction factors (catalysts, energy input, reactant). Recent this burgeoning field then comprehensively presented mechanisms nanosystems conferred theranostic functions discussed detail. It believed an emerging modality will play more important role

Language: Английский

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Polyphenol Health Effects on Cardiovascular and Neurodegenerative Disorders: A Review and Meta-Analysis

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(2), P. 351 - 351

Published: Jan. 16, 2019

Several studies have demonstrated that polyphenol-enriched diets may beneficial effects against the development of degenerative diseases, including atherosclerosis and disorders affecting central nervous system. This activity has been associated not only with antioxidant anti-inflammatory properties, but also additional mechanisms, such as modulation lipid metabolism gut microbiota function. However, long-term on humans provided controversial results, making prediction polyphenol impact health uncertain. The aim this review is to provide an overview critical analysis literature related principal dietary polyphenols cardiovascular neurodegenerative disorders. We critically considered meta-analyzed randomized controlled clinical trials involving subjects taking polyphenol-based supplements. Although some might improve specific markers risk cognitive status, many inconsistent data are present in literature. Therefore, definitive recommendations for use these compounds prevention disease decline currently applicable. Once pivotal aspects definition bioactivity, characterization pharmacokinetics safety, addressed, it will be possible a clear picture realistic potential prevention.

Language: Английский

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Lysine/RNA-interactions drive and regulate biomolecular condensation

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: July 2, 2019

Abstract Cells form and use biomolecular condensates to execute biochemical reactions. The molecular properties of non-membrane-bound are directly connected the amino acid content disordered protein regions. Lysine plays an important role in cellular function, but little is known about its condensation. Here we show that disorder abundant protein/RNA granules lysine enriched regions proteins P-bodies compared entire human proteome. Lysine-rich polypeptides phase separate into lysine/RNA-coacervates more dynamic differ at level from arginine/RNA-coacervates. Consistent with ability drive separation, lysine-rich variants Alzheimer’s disease-linked tau undergo coacervation RNA vitro bind stress cells. Acetylation reverses liquid–liquid separation reduces colocalization granules. Our study establishes as regulator

Language: Английский

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Formation of biological condensates via phase separation: Characteristics, analytical methods, and physiological implications

Journal of Biological Chemistry, Journal Year: 2019, Volume and Issue: 294(40), P. 14823 - 14835

Published: Aug. 23, 2019

Language: Английский

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Neurodegenerative Diseases – Is Metabolic Deficiency the Root Cause?

Frontiers in Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: March 31, 2020

Neurodegenerative diseases, including Alzheimer, Parkinson, Huntington, and amyotrophic lateral sclerosis, are a prominent class of neurological diseases currently without cure. They characterized by an inexorable loss specific type neurons. The selective vulnerability neuronal clusters (typically subcortical cluster) in the early stages, followed spread disease to higher cortical areas, is typical pattern progression. share range molecular cellular pathologies, protein aggregation, mitochondrial dysfunction, glutamate toxicity, calcium load, proteolytic stress, oxidative neuroinflammation, aging, which contribute death. Efforts treat these often limited fact that they tend address any one above pathological changes while ignoring others. Lack clarity regarding possible root cause underlies all pathologies poses significant challenge. In search integrative theory for neurodegenerative pathology, we hypothesize metabolic deficiency certain vulnerable common underlying thread links many dimensions disease. current review aims present outline such theory. We new perspective as disorders at molecular, cellular, systems levels. This helps understand mechanism facets may lead more promising disease-modifying therapeutic interventions. Here, briefly discuss also involvement glia vascular dysfunctions. Any failure satisfaction demand neurons triggers chain events precipitate various manifestations pathology.

Language: Английский

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Human cerebral organoids — a new tool for clinical neurology research

Nature Reviews Neurology, Journal Year: 2022, Volume and Issue: 18(11), P. 661 - 680

Published: Oct. 17, 2022

Language: Английский

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Caspase-9: A Multimodal Therapeutic Target With Diverse Cellular Expression in Human Disease

Frontiers in Pharmacology, Journal Year: 2021, Volume and Issue: 12

Published: July 9, 2021

Caspase-9, a cysteine-aspartic protease known for its role as an initiator of intrinsic apoptosis, regulates physiological cell death and pathological tissue degeneration. Its nonapoptotic functions, including regulation cellular differentiation/maturation, innate immunity, mitochondrial homeostasis, autophagy, reveal multimodal landscape caspase-9 functions in health disease. Recent work has demonstrated that can drive neurovascular injury through endothelial dysfunction. CASP9 polymorphisms have been linked with various cancers, neurological disorders, autoimmune pathologies lumbar disc Clinical reports suggest alterations expression, activity or function may be associated acute chronic neurodegeneration, retinal neuropathy, slow-channel myasthenic syndrome, disease, cardiomyopathies, atherosclerosis Healthy tissues maintain at low basal levels, rendering supraphysiological activation tractable target therapeutic interventions. Strategies selective inhibition include dominant negative mutants pharmacological inhibitors derived from the XIAP protein, whose Bir3 domain is endogenous highly inhibitor. However, mechanistic implications expression remain indeterminate many pathologies. By assembling clinical genetics, signaling localization human tissues, this review identifies gaps between experimental studies on caspase-9, presents opportunities further investigations to examine consequences caspase

Language: Английский

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Therapeutic Potential of Natural Products in Treating Neurodegenerative Disorders and Their Future Prospects and Challenges

Molecules, Journal Year: 2021, Volume and Issue: 26(17), P. 5327 - 5327

Published: Sept. 2, 2021

Natural products derived from plants, as well their bioactive compounds, have been extensively studied in recent years for therapeutic potential a variety of neurodegenerative diseases (NDs), including Alzheimer’s (AD), Huntington’s (HD), and Parkinson’s (PD) disease. These are characterized by progressive dysfunction loss neuronal structure function. There has little progress designing efficient treatments, despite impressive breakthroughs our understanding NDs. In the prevention therapy NDs, use natural may provide great opportunities; however, many clinical issues emerged regarding use, primarily based on lack scientific support or proof effectiveness patient safety. Since neurodegeneration is associated with myriad pathological processes, targeting multi-mechanisms action neuroprotection approaches that include preventing cell death restoring function damaged neurons should be employed. treatment AD PD, neuroprotective agents. This current review will highlight numerous compounds thatexert effects pathologies

Language: Английский

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