The heterogeneity of Parkinson’s disease

Journal of Neural Transmission, Journal Year: 2023, Volume and Issue: 130(6), P. 827 - 838

Published: May 11, 2023

The heterogeneity of Parkinson's disease (PD), i.e. the various clinical phenotypes, pathological findings, genetic predispositions and probably also implicated pathophysiological pathways pose a major challenge for future research projects therapeutic trail design. We outline several concepts, mechanisms, including presumed roles α-synuclein misfolding aggregation, Lewy bodies, oxidative stress, iron melanin, deficient autophagy processes, insulin incretin signaling, T-cell autoimmunity, gut-brain axis evidence that microbial (viral) agents may induce molecular hallmarks neurodegeneration. hypothesis is discussed, whether PD might indeed be triggered by exogenous (infectious) in susceptible individuals upon entry via olfactory bulb (brain first) or gut (body-first), which would support idea mechanisms change over time. unresolved have contributed to failure past trials, attempted slow course PD. thus conclude patients need personalized approaches tailored specific phenomenological etiologic subtypes disease.

Language: Английский

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The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(20), P. 12289 - 12289

Published: Oct. 14, 2022

The bidirectional interaction between the gut microbiota (GM) and Central Nervous System, so-called brain axis (GMBA), deeply affects function has an important impact on development of neurodegenerative diseases. In Parkinson’s disease (PD), gastrointestinal symptoms often precede onset motor non-motor manifestations, alterations in GM composition accompany pathogenesis. Several studies have been conducted to unravel role dysbiosis intestinal permeability PD progression, but therapeutic diagnostic applications modifying approaches remain be fully elucidated. After a brief introduction involvement GMBA disease, we present evidence for leaky patients. According these data, then review potential GM-based signatures serve as biomarkers highlight emerging probiotics, prebiotics, antibiotics, dietary interventions, fecal transplantation supportive PD. Finally, analyze mutual influence commonly prescribed medications gut-microbiota, offer insights also nasal oral pathology, thus providing comprehensive up-to-date overview microbial features diagnosis treatment.

Language: Английский

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The classical and non-classical axes of renin-angiotensin system in Parkinson disease: The bright and dark side of the moon

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 94, P. 102200 - 102200

Published: Jan. 17, 2024

Language: Английский

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Immunological shifts during early-stage Parkinson’s disease identified with DNA methylation data on longitudinally collected blood samples

npj Parkinson s Disease, Journal Year: 2024, Volume and Issue: 10(1)

Published: Jan. 11, 2024

Abstract Parkinson’s disease (PD) is the second most common neurodegenerative in United States. Decades before motor symptoms manifest, non-motor such as hyposmia and rapid eye movement (REM) sleep behavior disorder are highly predictive of PD. Previous immune profiling studies have identified alterations to proportions cells blood clinically defined PD patients. However, it remains unclear if these phenotypes manifest clinical diagnosis We utilized longitudinal DNA methylation (DNAm) microarray data from Progression Marker’s Initiative (PPMI) perform prodromal patients (Prod). previously reported changes neutrophil, monocyte, T cell numbers Additionally, we noted unrecognized decreases naive B compartment Prod patient group. Over time, observed proportion innate increased, but adaptive decreased. subsets associated with REM disturbances early cognitive decline. Lastly, increases memory both genetic ( LRRK2 genotype) infectious (cytomegalovirus seropositivity) risk factors Our analysis shows that peripheral system dynamic progresses. The study provides a platform understand how when occur whether intervention at particular stages may be therapeutically advantageous.

Language: Английский

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Virus-induced brain pathology and the neuroinflammation-inflammation continuum: the neurochemists view

Journal of Neural Transmission, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 23, 2024

Abstract Fascinatingly, an abundance of recent studies has subscribed to the importance cytotoxic immune mechanisms that appear increase risk/trigger for many progressive neurodegenerative disorders, including Parkinson’s disease (PD), Alzheimer’s (AD), amyotrophic lateral sclerosis, and multiple sclerosis. Events associated with neuroinflammatory cascades, such as ageing, immunologic dysfunction, eventually disruption blood–brain barrier “cytokine storm”, be orchestrated mainly through activation microglial cells communication neurons. The inflammatory processes prompt cellular protein dyshomeostasis. share a common feature marked by characteristic pathological hallmarks abnormal neuronal accumulation. These Lewy bodies contain misfolded α-synuclein aggregates in PD or case AD, they are Aβ deposits tau-containing neurofibrillary tangles. Subsequently, these further elicit neurotoxic events which contribute onset neurodegeneration its progression aggravation neuroinflammation. However, there is caveat exclusively linking neuroinflammation neurodegeneration, since it’s highly unlikely dysregulation only factor contributes manifestation disorders. It unquestionably complex interaction other factors genetics, age, environment. This endorses “multiple hit hypothesis”. Consequently, if host genetic susceptibility coupled age-related weakened system, this makes them more susceptible virus/bacteria-related infection. may trigger chronic leading dyshomeostasis accumulation, finally, lead destruction. Here, we differentiate “neuroinflammation” “inflammation” regard involvement barrier, seems intact but defect inflammation. There neuroinflammation-inflammation continuum virus-induced brain affection. Therefore, propose staging process, might developed adding blood- CSF parameters, their stage-dependent composition severeness grade. If so, suitable optimise therapeutic strategies fight beginning avoid inflammation at all.

Language: Английский

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Dopamine Transmission Imbalance in Neuroinflammation: Perspectives on Long-Term COVID-19

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5618 - 5618

Published: March 15, 2023

Dopamine (DA) is a key neurotransmitter in the basal ganglia, implicated control of movement and motivation. Alteration DA levels central Parkinson’s disease (PD), common neurodegenerative disorder characterized by motor non-motor manifestations deposition alpha-synuclein (α-syn) aggregates. Previous studies have hypothesized link between PD viral infections. Indeed, different cases parkinsonism been reported following COVID-19. However, whether SARS-CoV-2 may trigger process still matter debate. Interestingly, evidence brain inflammation has described postmortem samples patients infected SARS-CoV-2, which suggests immune-mediated mechanisms triggering neurological sequelae. In this review, we discuss role proinflammatory molecules such as cytokines, chemokines, oxygen reactive species modulating homeostasis. Moreover, review existing literature on possible mechanistic interplay SARS-CoV-2-mediated neuroinflammation nigrostriatal DAergic impairment, cross-talk with aberrant α-syn metabolism.

Language: Английский

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Overview of management of infection-related movement disorders with focus on specific-infections

Clinical Parkinsonism & Related Disorders, Journal Year: 2024, Volume and Issue: 10, P. 100233 - 100233

Published: Jan. 1, 2024

Infections are important treatable causes of secondary movement disorders (MD) that can have heterogeneous presentations. According to various studies, infection-related (IRMD) account for around 10-20% MD. Certain infections a predilection causing MD, and some MD phenomenologies, such as acute cerebellar ataxia opsoclonus-myoclonus-ataxia syndromes (OMAS), suggest strong possibility an underlying infectious cause. The pathophysiology is multifaceted, including direct neuronal damage due neurotropism, granulomas, abscesses structural damage, inflammatory autoimmune responses triggered by infections. Understanding the prevalence, spectrum, pattern these IRMD common responsible helps in early diagnosis, instituting appropriate, timely treatment, thereby improving overall prognosis avoiding unnecessary investigations. In this review, we aim provide brief overview associated with clinical presentations IRMD, their pathophysiology, approach focus on specific treatments prevalent IRMD.

Language: Английский

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Fibrinaloid Microclots and Atrial Fibrillation

Biomedicines, Journal Year: 2024, Volume and Issue: 12(4), P. 891 - 891

Published: April 17, 2024

Atrial fibrillation (AF) is a comorbidity of variety other chronic, inflammatory diseases for which fibrinaloid microclots are known accompaniment (and in some cases, cause, with mechanistic basis). Clots are, course, well-known consequence atrial fibrillation. We here ask the question whether seen plasma or serum may fact also be cause (or contributor to) development AF. consider ‘risk factors’ AF, and particular, exogenous stimuli such as infection air pollution by particulates, both to The external accompaniments bacterial (lipopolysaccharide lipoteichoic acids) viral (SARS-CoV-2 spike protein) infections stimulate when added vitro, microclots, amyloid proteins, can cytotoxic, inducing hypoxia/reperfusion means. Strokes thromboembolisms common consequences Consequently, taking systems approach, we review considerable evidence detail, leads us suggest that it likely well have an aetiological role This has significant therapeutic implications.

Language: Английский

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Cytokine activity in Parkinson’s disease

Neuronal Signaling, Journal Year: 2023, Volume and Issue: 7(4)

Published: Nov. 17, 2023

The contribution of the immune system to pathophysiology neurodegenerative Parkinson's disease (PD) is increasingly being recognised, with alterations in innate and adaptive arms underlying central peripheral inflammation PD. As chief modulators response, cytokines have been intensely studied field PD both terms trying understand their pathogenesis, if they may comprise much needed therapeutic targets for a no current modifying therapy. This review summarises knowledge on key implicated (TNFα, IL-6, IL-1β, IL-10, IL-4 IL-1RA) that can modulate pro-inflammatory anti-inflammatory effects. Cytokine activity clearly complicated process mediated by substantial cross-talk signalling pathways need balance pro- However, understanding cytokine hold promise unlocking new insight into how it be halted.

Language: Английский

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Neuromicrobiology Comes of Age: The Multifaceted Interactions between the Microbiome and the Nervous System

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: 15(16), P. 2957 - 2965

Published: Aug. 5, 2024

The past decade has seen an explosion in our knowledge about the interactions between gut microbiota, central nervous system, and immune system. gut-brain axis recently gained much attention due to its role regulating host physiology. This review explores recent findings concerning potential pathways linking initiation, pathophysiology, development of neurological disorders. Our objective this work is uncover causative factors pinpoint particular therapeutic targets that may facilitate translation experimental animal research into practical applications for human patients. We highlight three distinct yet interrelated mechanisms: (1) disruptions both intestinal blood-brain barriers, (2) persistent neuroinflammation, (3) vagus nerve.

Language: Английский

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