Decoding Neurodegeneration: A Review of Molecular Mechanisms and Therapeutic Advances in Alzheimer’s, Parkinson’s, and ALS

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12613 - 12613

Published: Nov. 24, 2024

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, ALS, and Huntington's, remain formidable challenges in medicine, with their relentless progression limited therapeutic options. These diseases arise from a web of molecular disturbances-misfolded proteins, chronic neuroinflammation, mitochondrial dysfunction, genetic mutations-that slowly dismantle neuronal integrity. Yet, recent scientific breakthroughs are opening new paths to intervene these once-intractable conditions. This review synthesizes the latest insights into underlying dynamics neurodegeneration, revealing how intertwined pathways drive course diseases. With an eye on most promising advances, we explore innovative therapies emerging cutting-edge research: nanotechnology-based drug delivery systems capable navigating blood-brain barrier, gene-editing tools like CRISPR designed correct harmful variants, stem cell strategies that not only replace lost neurons but foster neuroprotective environments. Pharmacogenomics is reshaping treatment personalization, enabling tailored align individual profiles, while diagnostics biomarkers ushering era early, precise disease detection. Furthermore, novel perspectives gut-brain axis sparking interest mounting evidence suggests microbiome modulation may play role reducing neuroinflammatory responses linked neurodegenerative progression. Taken together, advances signal shift toward comprehensive, personalized approach could transform care. By integrating techniques, this offers forward-looking perspective future where treatments aim just manage symptoms fundamentally alter progression, presenting renewed hope for improved patient outcomes.

Language: Английский

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Monoamine Oxidase Inhibitors in Toxic Models of Parkinsonism

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1248 - 1248

Published: Jan. 31, 2025

Monoamine oxidase inhibitors are widely used for the symptomatic treatment of Parkinson's disease (PD). They demonstrate antiparkinsonian activity in different toxin-based models induced by 6-hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and pesticides (rotenone paraquat). In some models, such as MPTP-induced PD, MAO prevent formation neurotoxin MPP+ from protoxin MPTP. Regardless toxin's nature, potent dopamine loss reduction, hydrogen peroxide, peroxide signaling, accumulation peroxide-derived reactive oxygen species responsible development oxidative stress. It becomes increasingly clear that metabolites (e.g., rasagiline metabolite 1-R-aminoindan) possess their own bio-pharmacological activities unrelated to parent compound. addition, various exhibit multitarget action, which MAO-independent effects prevail. This opens new prospects novel therapeutics based on simultaneous actions several prospective targets therapy PD.

Language: Английский

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Mitophagy in Neurodegenerative Diseases: Mechanisms of Action and the Advances of Drug Discovery

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Neurodegenerative diseases (NDDs), such as Parkinson's disease (PD) and Alzheimer's (AD), are devastating brain incurable at the moment. Increasing evidence indicates that NDDs associated with mitochondrial dysfunction. Mitophagy removes defective or redundant mitochondria to maintain cell homeostasis, whereas deficient mitophagy accelerates accumulation of damaged mediate pathologies NDDs. Therefore, targeting has become a valuable therapeutic pathway for treatment Several modulators have been shown ameliorate neurodegeneration in PD AD. However, it remains be further investigated other Here, we describe mechanism key signaling summarize roles on pathogenesis Further, underline development advances AD therapy, discuss challenges limitations existing modulators, provide guidelines exploration drug design.

Language: Английский

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Metformin Effect Against Rotenone-Induced Parkinsonism-Like Symptoms in a Mouse Model

Al-Rafidain Journal of Medical Sciences ( ISSN 2789-3219 ), Journal Year: 2025, Volume and Issue: 8(2), P. 47 - 52

Published: April 8, 2025

Background: Targeting problems in lipid metabolism for the treatment of Parkinson's disease (PD) has advanced significantly recent years through use medications like metformin (MET). In a mouse model rotenone-induced PD, MET, commonly prescribed antidiabetic medication, may have neuroprotective effect. Rotenone is an inhibitor mitochondrial complex I that can lead to PD and dopaminergic (DA) cell loss. Objective: To evaluate mechanisms behind MET effect possible additive benefits MET/levodopa-carbidopa (L-DOPA/carbidopa) parkinsonism male mice. Methods: Albino mice were given rotenone (1 mg/kg/48hr, subcutaneous) 17 days. Following administration rotenone, 30-day oral (500 mg/kg/day) was initiated. The on toxicity assessed by detection α-synuclein neuroinflammatory marker tumor necrosis factor-α (TNF-α), we also showed DOPA decarboxylase (DDC) levels plasma could detect using enzyme-linked immunosorbent assay (ELISA) kits. behavioral tests performed wire hanging, catalepsy, pole tests. Results: Metformin ameliorated deficits Parkinsonian model, decreased serum DDC reduced. Conclusions: alleviate Parkinson's-like symptoms model.

Language: Английский

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Alpha-Synuclein drives NURR1 and NLRP3 Inflammasome dysregulation in Parkinson's disease: From pathogenesis to potential therapeutic strategies

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 156, P. 114692 - 114692

Published: April 22, 2025

Language: Английский

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Safety Concerns in Neurological Clinical Trials: A Challenge That the FDA Must Resolve

Biomedicines, Journal Year: 2024, Volume and Issue: 12(12), P. 2918 - 2918

Published: Dec. 22, 2024

Background: Monoclonal antibodies approved by the FDA, lecanemab, donanemab, and aducanumab, are failing to meet expected efficacy treat early Alzheimer’s disease, aducanumab has been recalled. Methods: Recently, it was reported that clinical trials of these may have violated patient’s rights subjected them high, likely lethal risk. The challenge with developing neurological disorders is their poor blood–brain barrier (BBB) penetration if antibody must enter brain, resulting in almost negligible brain bioavailability, requiring high dosing can be toxic. Results: drugs should also reviewed, considering placebo effects, since all shown severe side effects not prevented responses. In this critical urgent advice I am suggesting a guideline amendment proof sufficient bioavailability at site action, where known. Conclusions: For cross barrier, there proven options such as conjugating transferrin protein, making its absence more questionable.

Language: Английский

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Special Issue “Mechanisms and Novel Therapeutic Approaches for Neurodegenerative Diseases”

Biomedicines, Journal Year: 2024, Volume and Issue: 12(11), P. 2554 - 2554

Published: Nov. 8, 2024

Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's (PD), and amyotrophic lateral sclerosis (ALS), are among the major health problems of elderly, represent a global challenge due to their increasing prevalence complex pathophysiological mechanisms [...].

Language: Английский

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