Neuroinflammation in Neurodegenerative Disorders: Current Knowledge and Therapeutic Implications

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(7), С. 3995 - 3995

Опубликована: Апрель 3, 2024

Neurodegenerative disorders (NDs) have become increasingly common during the past three decades. Approximately 15% of total population world is affected by some form NDs, resulting in physical and cognitive disability. The most NDs include Alzheimer’s disease, Parkinson’s amyotrophic lateral sclerosis, Huntington’s disease. Although are caused a complex interaction genetic, environmental, lifestyle variables, neuroinflammation known to be associated with all often leading permanent damage neurons central nervous system. Furthermore, numerous emerging pieces evidence demonstrated that inflammation not only supports progression but can also serve as an initiator. Hence, various medicines capable preventing or reducing been investigated ND treatments. While anti-inflammatory medicine has shown promising benefits several preclinical models, clinical outcomes questionable. In this review, we discuss their current treatment strategies, role pathophysiology use agents potential therapeutic option.

Язык: Английский

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Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases

Archives of Toxicology, Год журнала: 2024, Номер 98(3), С. 579 - 615

Опубликована: Янв. 24, 2024

Abstract This article provides an overview of the background knowledge ferroptosis in nervous system, as well key role nuclear factor E2-related 2 (Nrf2) regulating ferroptosis. The takes Alzheimer's disease (AD), Parkinson's (PD), Huntington's (HD), and amyotrophic lateral sclerosis (ALS) starting point to explore close association between Nrf2 ferroptosis, which is clear significant importance for understanding mechanism neurodegenerative diseases (NDs) based on oxidative stress (OS). Accumulating evidence links pathogenesis NDs. As progresses, damage antioxidant excessive OS, altered expression levels, especially inhibition by lipid peroxidation inhibitors adaptive enhancement signaling, demonstrate potential clinical significance detecting identifying targeted therapy neuronal loss mitochondrial dysfunction. These findings provide new insights possibilities treatment prevention

Язык: Английский

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Huntington’s Disease: Complex Pathogenesis and Therapeutic Strategies

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(7), С. 3845 - 3845

Опубликована: Март 29, 2024

Huntington’s disease (HD) arises from the abnormal expansion of CAG repeats in huntingtin gene (HTT), resulting production mutant protein (mHTT) with a polyglutamine stretch its N-terminus. The pathogenic mechanisms underlying HD are complex and not yet fully elucidated. However, mHTT forms aggregates accumulates abnormally neuronal nuclei processes, leading to disruptions multiple cellular functions. Although there is currently no effective curative treatment for HD, significant progress has been made developing various therapeutic strategies treat HD. In addition drugs targeting toxicity mHTT, therapy approaches that aim reduce expression HTT hold great promise therapy. This review provides an overview current treatments, discusses different strategies, aims facilitate future advancements field.

Язык: Английский

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Neuroinflammation and neurodegeneration in Huntington’s disease: genetic hallmarks, role of metals and organophosphates

Neurogenetics, Год журнала: 2025, Номер 26(1)

Опубликована: Янв. 17, 2025

Язык: Английский

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Polyglutamine (PolyQ) Diseases: Navigating the Landscape of Neurodegeneration

ACS Chemical Neuroscience, Год журнала: 2024, Номер 15(15), С. 2665 - 2694

Опубликована: Июль 12, 2024

Polyglutamine (polyQ) diseases are a group of inherited neurodegenerative disorders caused by expanded cytosine-adenine-guanine (CAG) repeats encoding proteins with abnormally polyglutamine tract. A total nine polyQ have been identified, including Huntington's disease, six spinocerebellar ataxias, dentatorubral pallidoluysian atrophy (DRPLA), and spinal bulbar muscular (SBMA). The this class each considered rare, yet constitute the largest monogenic disorders. While subtype has its own causative gene, certain pathologic molecular attributes implicated in virtually all diseases, protein aggregation, proteolytic cleavage, neuronal dysfunction, transcription dysregulation, autophagy impairment, mitochondrial dysfunction. Although animal models disease available helping to understand their pathogenesis access disease-modifying therapies, there is neither cure nor prevention for these only symptomatic treatments available. In paper, we analyze data from CAS Content Collection summarize research progress diseases. We examine publication landscape area effort provide insights into current knowledge advances developments. review most discussed concepts assess strategies combat Finally, inspect clinical applications products against development pipelines. objective broad overview evolving regarding outline challenges, evaluate growth opportunities further efforts combating

Язык: Английский

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Exploring molecular mechanisms, therapeutic strategies, and clinical manifestations of Huntington’s disease

Archives of Pharmacal Research, Год журнала: 2024, Номер 47(6), С. 571 - 595

Опубликована: Май 19, 2024

Язык: Английский

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Unraveling the Puzzle of Therapeutic Peptides: A Promising Frontier in Huntington’s Disease Treatment

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(2), С. 783 - 815

Опубликована: Янв. 11, 2024

Huntington's disease (HD) is a neurodegenerative genetic disorder characterized by mutation in the huntingtin (HTT) gene, resulting production of mutant protein (mHTT). The accumulation mHTT leads to development toxic aggregates neurons, causing cell dysfunction and, eventually, death. Peptide therapeutics target various aspects HD pathology, including reduction and aggregation inhibition, extended CAG mRNA degradation, modulation dysregulated signaling pathways, such as BDNF/TrkB signaling. In addition, these peptide also detrimental interactions with InsP3R1, CaM, or Caspase-6 proteins mitigate HD. This Perspective provides detailed perspective on anti-HD therapeutic peptides, highlighting their design, structural characteristics, neuroprotective effects, specific mechanisms action. for exhibit promise preclinical models, but further investigation required confirm effectiveness viable strategies, recognizing that no approved therapy currently exists.

Язык: Английский

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Huntington’s Disease: Latest Frontiers in Therapeutics

Current Neurology and Neuroscience Reports, Год журнала: 2024, Номер 24(8), С. 255 - 264

Опубликована: Июнь 11, 2024

Язык: Английский

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Therapeutic Strategies in Huntington’s Disease: From Genetic Defect to Gene Therapy

Biomedicines, Год журнала: 2022, Номер 10(8), С. 1895 - 1895

Опубликована: Авг. 5, 2022

Despite the identification of an expanded CAG repeat on exon 1 huntingtin gene located chromosome as genetic defect causing Huntington’s disease almost 30 years ago, currently approved therapies provide only limited symptomatic relief and do not influence age onset or progression rate. Research has identified various intricate pathogenic cascades which lead to neuronal degeneration, but interfering with these mechanisms have been marked by many failures remain be validated. Exciting new opportunities are opened emerging techniques target mutant protein DNA RNA, allowing for “gene editing”. Although some issues relating “off-target” effects immune-mediated side need solved, strategies, combined stem cell more traditional approaches targeting specific cascades, such excitotoxicity bioavailability neurotrophic factors, could significant improvement outcomes treated patients.

Язык: Английский

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Huntington’s Disease Drug Development: A Phase 3 Pipeline Analysis

Pharmaceuticals, Год журнала: 2023, Номер 16(11), С. 1513 - 1513

Опубликована: Окт. 24, 2023

Huntington’s Disease (HD) is a severely debilitating neurodegenerative disorder in which sufferers exhibit different combinations of movement disorders, dementia, and behavioral or psychiatric abnormalities. The result trinucleotide repeat expansion mutation that inherited an autosomal dominant manner. While there currently no treatment to alter the course HD, are medications lessen abnormal symptoms. ClinicalTrials.gov was searched identify drugs have completed phase III drug trials for HD. described were further limited interventional studies recruiting, active not completed. In addition, all must posted update within past year. PubMed used gather information on these studies. Of nine clinical met criteria, eight involved following drugs: metformin, dextromethorphan/quinidine, deutetrabenazine, valbenazine, Cellavita pridopidine, SAGE-718, RO7234292 (RG6042). treatments, four already FDA approved. This systematic review provides resource summarizes present therapies treating this devastating condition United States.

Язык: Английский

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