Ageing as a risk factor for neurodegenerative disease

Nature Reviews Neurology, Journal Year: 2019, Volume and Issue: 15(10), P. 565 - 581

Published: Sept. 9, 2019

Language: Английский

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The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(24), P. 9739 - 9739

Published: Dec. 20, 2020

Matrix metalloproteinases (MMPs) are a family of zinc-dependent extracellular matrix (ECM) remodeling endopeptidases that have the capacity to degrade almost every component ECM. The degradation ECM is great importance, since it related embryonic development and angiogenesis. It also involved in cell repair tissues. When expression MMPs altered, can generate abnormal This initial cause chronic degenerative diseases vascular complications generated by diabetes. In addition, this process has an association with neurodegeneration cancer progression. Within ECM, tissue inhibitors (TIMPs) inhibit proteolytic activity MMPs. TIMPs important regulators turnover, remodeling, cellular behavior. Therefore, (similar MMPs) modulate angiogenesis, proliferation, apoptosis. An interruption balance between been implicated pathophysiology progression several diseases. review focuses on participation both (e.g., MMP-2 MMP-9) TIMP-1 TIMP-3) physiological processes how their regulation associated human inclusion current strategies mechanisms MMP inhibition new therapies targeting was considered.

Language: Английский

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Challenges in the diagnosis of Parkinson's disease

The Lancet Neurology, Journal Year: 2021, Volume and Issue: 20(5), P. 385 - 397

Published: April 21, 2021

Language: Английский

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Update on treatments for nonmotor symptoms of Parkinson's disease—an evidence‐based medicine review

Movement Disorders, Journal Year: 2019, Volume and Issue: 34(2), P. 180 - 198

Published: Jan. 17, 2019

ABSTRACT Objective To update evidence‐based medicine recommendations for treating nonmotor symptoms in Parkinson's disease (PD). Background The International Parkinson and Movement Disorder Society Evidence‐Based Medicine Committee's treatments of PD were first published 2002, updated 2011, now again through December 31, 2016. Methods Level I studies testing pharmacological, surgical, or nonpharmacological interventions the treatment reviewed. Criteria inclusion quality scoring as previously reported. disorders covered a range neuropsychiatric symptoms, autonomic dysfunction, sleep wakefulness, pain, fatigue, impaired olfaction, ophthalmologic dysfunction. Clinical efficacy, implications clinical practice, safety conclusions are Results A total 37 new qualified review. There no randomized controlled trials that met criteria anxiety disorders, rapid eye movement behavior disorder, excessive sweating, We identified clinically useful possibly depression, apathy, impulse control related dementia, psychosis, insomnia, daytime sleepiness, drooling, orthostatic hypotension, gastrointestinal urinary erectile pain. to treat non‐dementia‐level cognitive impairment. Conclusions evidence base has grown substantially recent years. However, options overall remain limited given high prevalence adverse impact these so development remains top priority. © 2019 Authors. Disorders by Wiley Periodicals, Inc. on behalf Society.

Language: Английский

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Parkinson Disease Epidemiology, Pathology, Genetics, and Pathophysiology

Clinics in Geriatric Medicine, Journal Year: 2019, Volume and Issue: 36(1), P. 1 - 12

Published: Aug. 24, 2019

Language: Английский

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International Parkinson and movement disorder society evidence‐based medicine review: Update on treatments for the motor symptoms of Parkinson's disease

Movement Disorders, Journal Year: 2018, Volume and Issue: 33(8), P. 1248 - 1266

Published: March 23, 2018

The objective of this review was to update evidence-based medicine recommendations for treating motor symptoms Parkinson's disease (PD).The Movement Disorder Society Evidence-Based Medicine Committee treatments PD were first published in 2002 and updated 2011, we continued the December 31, 2016.Level I studies interventions reviewed. Criteria inclusion quality scoring as previously reported. Five clinical indications considered, conclusions regarding implications practice are reported.A total 143 new qualified. There no clinically useful prevent/delay progression. For monotherapy early PD, nonergot dopamine agonists, oral levodopa preparations, selegiline, rasagiline useful. adjunct therapy early/stable rasagiline, zonisamide optimized general or specific including gait, rivastigmine is possibly physiotherapy useful; exercise-based movement strategy training formalized patterned exercises changes prevention/delay complications. fluctuations, most pergolide, ER, intestinal infusion, entacapone, opicapone, zonisamide, safinamide, bilateral STN GPi DBS dyskinesia, amantadine, clozapine, useful.The options continues expand. These allow physician determine which intervention recommend an individual patient. © 2018 International Parkinson Society.

Language: Английский

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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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Parkinson’s disease: etiopathogenesis and treatment

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2020, Volume and Issue: 91(8), P. 795 - 808

Published: June 23, 2020

The concept of ‘idiopathic’ Parkinson’s disease (PD) as a single entity has been challenged with the identification several clinical subtypes, pathogenic genes and putative causative environmental agents. In addition to classic motor symptoms, non-motor manifestations (such rapid eye movement sleep disorder, anosmia, constipation depression) appear at prodromic/premotor stage evolve, along cognitive impairment dysautonomia, progresses, often dominating advanced stages disease. key molecular mechanisms include α-synuclein misfolding aggregation, mitochondrial dysfunction, protein clearance (associated deficient ubiquitin-proteasome autophagy-lysosomal systems), neuroinflammation oxidative stress. involvement dopaminergic well noradrenergic, glutamatergic, serotonergic adenosine pathways provide insights into rich variable phenomenology associated PD possibility alternative therapeutic approaches beyond traditional dopamine replacement therapies. One biggest challenges in development potential neuroprotective therapies lack reliable sensitive biomarkers progression. Immunotherapies such use vaccination or monoclonal antibodies directed against aggregated, toxic α-synuclein.as anti-aggregation strategies are currently investigated trials. application glucagon-like peptide one receptor agonists, specific gene target agents GBA LRRK2 modifiers) other modifying drugs cautious optimism that more effective on horizon. Emerging therapies, new symptomatic drugs, innovative drug delivery systems novel surgical interventions give hope patients about their future outcomes prognosis.

Language: Английский

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Parkinson disease-associated cognitive impairment

Nature Reviews Disease Primers, Journal Year: 2021, Volume and Issue: 7(1)

Published: July 1, 2021

Language: Английский

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Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodegeneration in mice

Science Translational Medicine, Journal Year: 2018, Volume and Issue: 10(465)

Published: Oct. 31, 2018

Parkinson's disease (PD) is characterized by a profound loss of dopaminergic neurons in the substantia nigra, accompanied chronic neuroinflammation, mitochondrial dysfunction, and widespread accumulation α-synuclein-rich protein aggregates form Lewy bodies. However, mechanisms linking α-synuclein pathology neuronal death to microglial neuroinflammation have not been completely elucidated. We show that activation NLR family pyrin domain containing 3 (NLRP3) inflammasome common pathway triggered both fibrillar degeneration absence aggregates. Cleaved caspase-1 adaptor apoptosis-associated speck-like C-terminal caspase recruitment (ASC) were elevated nigra brains patients with PD multiple preclinical models. NLRP3 mouse microglia resulted delayed but robust leading extracellular interleukin-1β ASC release pyroptosis. Nanomolar doses small-molecule inhibitor, MCC950, abolished α-synuclein-mediated cells release. Furthermore, oral administration MCC950 rodent models inhibited effectively mitigated motor deficits, nigrostriatal degeneration, These findings suggest may be sustained source could drive progressive neuropathology highlight as potential target for disease-modifying treatments PD.

Language: Английский

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