The pathogenesis of Parkinson's disease

The Lancet, Journal Year: 2024, Volume and Issue: 403(10423), P. 293 - 304

Published: Jan. 1, 2024

Language: Английский

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Flavonoids: Their putative neurologic roles, epigenetic changes, and gut microbiota alterations in Parkinson’s disease

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115788 - 115788

Published: Oct. 31, 2023

Parkinson's Disease (PD), a neurodegenerative disorder, is characterized by the degeneration of progressive dopaminergic (DA) neurons in substantia nigra region human midbrain. Although just what causes PD remains mystery, it known that oxidative stress (OS) as well mitochondrial dysfunction, neuro-inflammation, and insufficient neurotrophic support play role disease's pathophysiology. Phytochemicals are diverse small molecule group derived from plants can be classified into numerous classes on basis their biological activities chemical structure. Of these groups phytochemicals, most abundant, which has well-established anti-Parkinson's effects, polyphenols. Flavonoids, including naringin naringenin, genistein, kaempferol, anthocyanins, epigallocatechin-3-gallate, baicalein plant-based biologically active polyphenols, have been shown to exhibit therapeutic potential when used treatment for variety pathological illnesses, such diseases (NDs) PD. Recently, was reported flavonoids beneficial effects PD, protection DA neurons, improvement motor cognitive abilities, regulation signaling pathways, modulation OS neuro-inflammation. In addition, changing composition bacteria gut microbiota, reduce pathogenic strains promote growth strains. this context, current paper will provide literature review neurological roles play, one abundant phytochemical families,

Language: Английский

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Pathogenesis of DJ-1/PARK7-Mediated Parkinson’s Disease

Cells, Journal Year: 2024, Volume and Issue: 13(4), P. 296 - 296

Published: Feb. 6, 2024

Parkinson’s disease (PD) is a common movement disorder associated with the degeneration of dopaminergic neurons in substantia nigra pars compacta. Mutations PD-associated gene PARK7 alter structure and function encoded protein DJ-1, resulting autosomal recessively inherited increases risk developing PD. DJ-1 was first discovered 1997 as an oncogene early-onset PD 2003. account for approximately 1% all occurrences, functions have been studied extensively. In healthy subjects, acts antioxidant oxidative stress sensor several neuroprotective mechanisms. It also involved mitochondrial homeostasis, regulation apoptosis, chaperone-mediated autophagy (CMA), dopamine homeostasis by regulating various signaling pathways, transcription factors, molecular chaperone functions. While protects against damaging reactive oxygen species, neurotoxins, mutant α-synuclein, mutations may lead to inefficient neuroprotection progression As current therapies treat only symptoms PD, development that directly inhibit stress-induced neuronal cell death critical. has proposed potential therapeutic target, while oxidized could operate biomarker this paper, we review role pathogenesis highlighting some its key consequences dysfunction.

Language: Английский

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Evolving Landscape of Parkinson’s Disease Research: Challenges and Perspectives

ACS Omega, Journal Year: 2025, Volume and Issue: 10(2), P. 1864 - 1892

Published: Jan. 8, 2025

Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily affects movement. It occurs due to gradual deficit of dopamine-producing brain cells, particularly in the substantia nigra. The precise etiology PD not fully understood, but it likely involves combination genetic and environmental factors. therapies available at present alleviate symptoms do stop disease's advancement. Research endeavors are currently directed inventing disease-controlling aim inherent mechanisms PD. biomarker breakthroughs hold enormous potential: earlier diagnosis, better monitoring, targeted treatment based on individual response could significantly improve patient outcomes ease burden this disease. research an active evolving field, focusing understanding mechanisms, identifying biomarkers, developing new treatments, improving care. In report, we explore data from CAS Content Collection outline progress We analyze publication landscape offer perspective into latest expertise advancements. Key emerging concepts reviewed strategies fight evaluated. Pharmacological targets, risk factors, as well comorbid diseases explored, clinical usage products against with their production pipelines trials for drug repurposing examined. This review aims comprehensive overview advancing current about PD, define challenges, assess growth prospects stimulate efforts battling

Language: Английский

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Oxidative stress and synaptic dysfunction in rodent models of Parkinson's disease

Neurobiology of Disease, Journal Year: 2022, Volume and Issue: 173, P. 105851 - 105851

Published: Aug. 23, 2022

Parkinson's disease (PD) is a multifactorial disorder involving complex interplay between variety of genetic and environmental factors. In this scenario, mitochondrial impairment oxidative stress are widely accepted as crucial neuropathogenic mechanisms, also evidenced by the identification PD-associated genes that directly involved in function. The concept dysfunction closely linked to synaptic dysfunction. Indeed, compelling evidence supports role mitochondria transmission plasticity, although many aspects have not yet been fully elucidated. Here, we will provide brief overview most relevant obtained different neurotoxin-based rodent models PD, focusing on synaptopathy, an early central event preceding overt nigrostriatal neurodegeneration. deficits occurring PD pathogenesis view development potential disease-modifying therapeutic strategies.

Language: Английский

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Autophagy in Parkinson’s Disease

Biomolecules, Journal Year: 2023, Volume and Issue: 13(10), P. 1435 - 1435

Published: Sept. 22, 2023

Parkinson’s disease (PD) is a devastating associated with accumulation of α-synuclein (α-Syn) within dopaminergic neurons, leading to neuronal death. PD characterized by both motor and non-motor clinical symptoms. Several studies indicate that autophagy, an important intracellular degradation pathway, may be involved in different neurodegenerative diseases including PD. The autophagic process mediates the protein aggregates, damaged unneeded proteins, organelles, allowing their clearance, thereby maintaining cell homeostasis. Impaired autophagy cause abnormal proteins. Incomplete or impaired explain neurotoxic aggregates several Indeed, have suggested contribution α-Syn accumulation, death neuroinflammation. In this review, we summarize recent literature on involvement pathogenesis.

Language: Английский

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Parkinson’s disease-associated ATP13A2/PARK9 functions as a lysosomal H+,K+-ATPase

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 20, 2023

Abstract Mutations in the human ATP13A2 (PARK9), a lysosomal ATPase, cause Kufor-Rakeb Syndrome, an early-onset form of Parkinson’s disease (PD). Here, we demonstrate that functions as H + ,K -ATPase. The K -dependent ATPase activity and -transport are inhibited by inhibitor sarco/endoplasmic reticulum Ca 2+ -ATPase, thapsigargin, -competitive inhibitors gastric such vonoprazan SCH28080. Interestingly, these -ATPase alkalinization α-synuclein accumulation, which pathological hallmarks PD. Furthermore, PD-associated mutants show abnormal expression function. Our results suggest /K -transporting function contributes to acidification degradation lysosomes.

Language: Английский

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DNA Damage and Parkinson’s Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4187 - 4187

Published: April 10, 2024

The etiology underlying most sporadic Parkinson's' disease (PD) cases is unknown. Environmental exposures have been suggested as putative causes of the disease. In cell models and in animal studies, certain chemicals can destroy dopaminergic neurons. However, mechanisms how these cause death neurons not understood. Several agents are mitochondrial toxins that inhibit complex I electron transport chain. Familial PD genes also encode proteins with important functions mitochondria. Mitochondrial dysfunction respiratory chain, combination presence redox active dopamine molecules cells, will lead to accumulation reactive oxygen species (ROS) Here, propose a mechanism regarding ROS may killing specificity for One rarely considered hypothesis produced by defective mitochondria formation oxidative DNA damage nuclear DNA. Many neuron-specific extraordinary long, ranging size from several hundred kilobases well over megabase. It predictable such long contain large numbers damaged bases, example form 8-oxoguanine (8-oxoG), which major type ROS. These lesions slow down or stall progression RNA polymerase II, term referred transcription stress. Furthermore, ROS-induced mutations, even postmitotic cells impaired mutagenesis loss neuronal integrity, eventually leading during human lifetime.

Language: Английский

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Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 69 - 69

Published: Jan. 7, 2025

Ubiquitination is cells' second most abundant posttranslational protein modification after phosphorylation. The ubiquitin-proteasome system (UPS) critical in maintaining essential life processes such as cell cycle control, DNA damage repair, and apoptosis. Mutations ubiquitination pathway genes are strongly linked to the development spread of multiple cancers since several UPS family members possess oncogenic or tumor suppressor activities. This comprehensive review delves into understanding ubiquitin code, shedding light on its role cancer biology immune evasion. Furthermore, we highlighted recent advances field for targeting effective therapeutic intervention against human cancers. We also discussed update small-molecule inhibitors PROTACs their progress preclinical clinical trials.

Language: Английский

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Biomarkers in Neurodegenerative Diseases: Proteomics Spotlight on ALS and Parkinson’s Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(16), P. 9299 - 9299

Published: Aug. 18, 2022

Neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) are both characterized by pathogenic protein aggregates that correlate with the progressive degeneration of neurons loss behavioral functions. Both lack biomarkers for diagnosis treatment efficacy. Proteomics is an unbiased quantitative tool capable high throughput quantitation thousands proteins from minimal sample volumes. We review recent proteomic studies in human tissues, plasma, cerebrospinal fluid (CSF), exosomes ALS PD identify potential utility biomarkers. Further, we disease-related post-translational modifications key TDP43 α-synuclein studies, which may serve compare relative absolute approaches biomarker discuss technological advancements suitable early-diagnosis efficacy these diseases.

Language: Английский

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