The epidemiology of Parkinson's disease

The Lancet, Journal Year: 2024, Volume and Issue: 403(10423), P. 283 - 292

Published: Jan. 1, 2024

Language: Английский

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Incidence of Parkinson disease in North America

npj Parkinson s Disease, Journal Year: 2022, Volume and Issue: 8(1)

Published: Dec. 15, 2022

Abstract Parkinson disease (PD) is the second most common age-related neurodegenerative condition diagnosed in North America. We recently demonstrated, using multiple epidemiological data sources, that prevalence of PD diagnoses was greater than previously reported and currently used for clinical, research, policy decision-making. Prior incidence estimates have varied, unclear reasons. There a need improved incidence, not only care delivery planning future but also increasing our understanding risk. The objective this study thus to investigate across five cohorts America year, 2012. contained on 6.7 million person-years adults ages 45 older, 9.3 65 older. Our age-sex-adjusted ranged from 108 212 per 100,000 among persons 47 77 100,00 increased with age higher males. found persistent spatial clustering incident U.S. varied part due case ascertainment diagnosis methods, possibly influence population factors (prevalence genetic risk or protective markers) geographic location (exposure environmental toxins). Understanding source these variations will be important health policy, planning.

Language: Английский

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Alpha-Synuclein Aggregation Pathway in Parkinson’s Disease: Current Status and Novel Therapeutic Approaches

Cells, Journal Year: 2022, Volume and Issue: 11(11), P. 1732 - 1732

Published: May 24, 2022

Following Alzheimer’s, Parkinson’s disease (PD) is the second-most common neurodegenerative disorder, sharing an unclear pathophysiology, a multifactorial profile, and massive social costs worldwide. Despite this, no disease-modifying therapy available. PD tightly associated with α-synuclein (α-Syn) deposits, which become organised into insoluble, amyloid fibrils. As typical intrinsically disordered protein, α-Syn adopts monomeric, random coil conformation in aqueous solution, while its interaction lipid membranes drives transition of molecule part α-helical structure. The central unstructured region involved fibril formation by converting to well-defined, β-sheet rich secondary structures. Presently, most therapeutic strategies against are focused on designing small molecules, peptides, peptidomimetics that can directly target aggregation pathway. Other approaches include gene silencing, cell transplantation, stimulation intracellular clearance autophagy promoters, degradation pathways based immunotherapy In present review, we sum marise current advances related aggregation/neurotoxicity. These findings valuable arsenal for further development efficient, nontoxic, non-invasive protocols tackles onset progression future.

Language: Английский

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Levodopa-Induced Dyskinesia in Parkinson’s Disease: Pathogenesis and Emerging Treatment Strategies

Cells, Journal Year: 2022, Volume and Issue: 11(23), P. 3736 - 3736

Published: Nov. 23, 2022

The most commonly used treatment for Parkinson’s disease (PD) is levodopa, prescribed in conjunction with carbidopa. Virtually all patients PD undergo dopamine replacement therapy using levodopa during the course of disease’s progression. However, despite fact that “gold standard” treatments and has ability to significantly alleviate symptoms, it comes side effects advanced PD. Levodopa remains current clinical choice patients, but approximately 80% treated develop levodopa-induced dyskinesia (LID) stages disease. A better understanding pathological mechanisms LID possible means improvement would improve outcome reduce complexity medication use, lower adverse effects, thus, improving quality life prolonging their cycle. This review assesses recent advancements underlying therapeutic management options available after emergence patients. We summarized pathogenesis new LID-related concluded targeting pathways other than dopaminergic pathway treat become a possibility, and, currently, amantadine, drugs 5-hydroxytryptamine receptors, surgery can target symptoms caused by LID.

Language: Английский

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Neurodegenerative disorders: Mechanisms of degeneration and therapeutic approaches with their clinical relevance

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 99, P. 102357 - 102357

Published: June 1, 2024

Neurodegenerative disorders (NDs) are expected to pose a significant challenge for both medicine and public health in the upcoming years due global demographic changes. NDs mainly represented by degeneration/loss of neurons, which is primarily accountable severe mental illness. This neuronal degeneration leads many neuropsychiatric problems permanent disability an individual. Moreover, tight junction brain, blood-brain barrier (BBB)has protective feature, functioning as biological that can prevent medicines, toxins, foreign substances from entering brain. However, delivering any medicinal agent brain (i.e., Multiple sclerosis, Alzheimer's, Parkinson's, etc.) enormously challenging. There approved therapies address NDs, but most them only help treat associated manifestations. The available have failed control progression certain factors, i.e., BBB drug-associated undesirable effects. extremely complex pathology, with pathogenic mechanisms involved initiation progression; thereby, limited survival rate has been observed ND patients. Hence, understanding exact mechanism behind crucial developing alternative approaches improving patients' rates. Thus, present review sheds light on different cellular novel therapeutic their clinical relevance, will assist researchers alternate strategies limitations conventional therapies. current work offers scope into near future improve approach NDs.

Language: Английский

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Parkinson’s Disease Is Predominantly an Environmental Disease

Journal of Parkinson s Disease, Journal Year: 2024, Volume and Issue: 14(3), P. 451 - 465

Published: Jan. 12, 2024

Parkinson’s disease is the world’s fastest growing brain disorder, and exposure to environmental toxicants principal reason. In this paper, we consider alternative, but unsatisfactory, explanations for its rise, including improved diagnostic skills, aging populations, genetic causes. We then detail three that are likely among main causes of disease— certain pesticides, solvent trichloroethylene, air pollution. All ubiquitous, many affect mitochondrial functioning, all can access humans via various routes, inhalation ingestion. reach hopeful conclusion most thus preventable help create a world where increasingly rare.

Language: Английский

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A Comprehensive Review on Advancements in Artificial Intelligence Approaches and Future Perspectives for Early Diagnosis of Parkinson's Disease

International Journal of Mathematics Statistics and Computer Science, Journal Year: 2024, Volume and Issue: 2, P. 173 - 182

Published: Jan. 26, 2024

Parkinson's disease (PD) is a neurological condition that generally strikes people in their average age of onset for PD disorder, 55 and up. A wide variety motor non-motor symptoms can be observed patients with PD. The medical community has made great strides recent years, but still no treatment or cure. Therefore, exploring possible ways early identification an intriguing scientific endeavor. Full may not appear years due to the progressive nature Thus, diagnosis vital enhance patient's quality life. Symptoms will usually worsen time, so keep mind. Several neurodegenerative disorders share very similar symptoms, making crucial prediction. Many are starting pay attention using Artificial Intelligence (AI) methods diagnostics because they process massive volumes data make reliable statistical predictions. This paper covers all bases when it comes artificial intelligence approaches diagnosis, including many deep machine learning-based have been deployed how opened new avenues research. Furthermore, study explores current situation future possibilities data-driven AI diagnosis. excellent resource as review article researchers interested creating prediction models employing different AI-based modalities.

Language: Английский

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Role of the Exposome in Neurodegenerative Disease: Recent Insights and Future Directions

Annals of Neurology, Journal Year: 2024, Volume and Issue: 95(4), P. 635 - 652

Published: Feb. 27, 2024

Neurodegenerative diseases are increasing in prevalence and place a significant burden on society. The causes multifactorial complex, evidence suggests dynamic interplay between genes the environment, emphasizing importance of identifying understanding role lifelong exposures, known as exposome, nervous system. This review provides an overview recent advances toward defining neurodegenerative disease exposomes, focusing Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease. We present current state field based emerging data, elaborate key themes potential mechanisms, conclude with limitations future directions. ANN NEUROL 2024;95:635-652.

Language: Английский

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New insights in animal models of neurotoxicity-induced neurodegeneration

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Jan. 8, 2024

The high prevalence of neurodegenerative diseases is an unintended consequence the longevity population, together with lack effective preventive and therapeutic options. There great pressure on preclinical research, both old new models are required to increase pipeline drugs for clinical testing. We review here main neurotoxicity-based animal leading central neurodegeneration. Our focus was studying how changes in neurotransmission neuroinflammation, mainly rodent models, contribute harmful processes linked majority currently use mimic Parkinson's disease (PD) Alzheimer's (AD), which most common conditions older adults. AD age-related dementia, whereas PD movement disorder also cases dementia. Several natural toxins xenobiotic agents induce dopaminergic neurodegeneration can reproduce neuropathological traits PD. literature analysis MPTP, 6-OH-dopamine, rotenone suggested latter as a useful model when specific doses were administrated systemically C57BL/6 mice. Cholinergic modelled toxin scopolamine, screening protective against cognitive decline AD. have been used neuroinflammation-based dementia AD, including lipopolysaccharide (LPS), streptozotocin, monomeric C-reactive protein. bacterial agent LPS makes testing anti-inflammatory therapies halt development severity However, neurotoxin might be more than genetic drug discovery but that not case where they cannot beat developments transgenic mouse models. Overall, we should work using all available either

Language: Английский

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Leucine-Rich Repeat Kinases

Annual Review of Biochemistry, Journal Year: 2024, Volume and Issue: 93(1), P. 261 - 287

Published: April 15, 2024

Activating mutations in leucine-rich repeat kinase 2 (LRRK2) represent the most common cause of monogenic Parkinson's disease. LRRK2 is a large multidomain protein that phosphorylates specific subset ∼65 human Rab GTPases, which are master regulators secretory and endocytic pathways. After phosphorylation by LRRK2, Rabs lose capacity to bind cognate effector proteins guanine nucleotide exchange factors. Moreover, phosphorylated cannot interact with their prenyl-binding retrieval (also known as dissociation inhibitors) and, thus, they become trapped on membrane surfaces. Instead, gain phospho-Rab-specific proteins, such RILPL1, resulting pathological consequences. also act upstream controlling its activation recruitment onto membranes. signaling counteracted phosphoprotein phosphatase PPM1H, selectively dephosphorylates phospho-Rab proteins. We present here our current understanding structure, biochemical properties, cell biology related paralog LRRK1 discuss how this information guides generation inhibitors for potential benefit patients.

Language: Английский

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