Parkinson's Disease: Is It a Toxic Syndrome?

Parkinson's disease (PD) is one of the neurodegenerative diseases which we can by certainty identify its pathology, however, this confidence disappeares when talking about the cause. A long history of trials, suggestions, and theories tried linking PD to a specific causation. In this paper, a new suggestion is trying to find its way, could it be toxicology? Can we—in the future—look to PD as an occupational disease, in fact, many clues point to the possible toxic responsibility—either total or partial—in causing this disease. Searching for possible toxic causes for PD would help in designing perfect toxic models in animals.

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Can SARS-CoV-2 Infection Lead to Neurodegeneration and Parkinson’s Disease?

Brain Sciences ◽

10.3390/brainsci11121654 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1654

Author(s):

Lea Krey ◽

Meret Koroni Huber ◽

Günter U. Höglinger ◽

Florian Wegner

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neurodegenerative Diseases ◽

Viral Infection ◽

Daily Life ◽

Psychosocial Impact ◽

Worldwide Population ◽

Current Topic ◽

The Future

The SARS-CoV-2 pandemic has affected the daily life of the worldwide population since 2020. Links between the newly discovered viral infection and the pathogenesis of neurodegenerative diseases have been investigated in different studies. This review aims to summarize the literature concerning COVID-19 and Parkinson’s disease (PD) to give an overview on the interface between viral infection and neurodegeneration with regard to this current topic. We will highlight SARS-CoV-2 neurotropism, neuropathology and the suspected pathophysiological links between the infection and neurodegeneration as well as the psychosocial impact of the pandemic on patients with PD. Some evidence discussed in this review suggests that the SARS-CoV-2 pandemic might be followed by a higher incidence of neurodegenerative diseases in the future. However, the data generated so far are not sufficient to confirm that COVID-19 can trigger or accelerate neurodegenerative diseases.

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Molecular imaging of gene therapy. The future in Parkinson's disease therapy?

Aktuelle Neurologie ◽

10.1055/s-2005-919237 ◽

2005 ◽

Vol 32 (S 4) ◽

Author(s):

A.H Jacobs ◽

R Hilker ◽

L Burghaus ◽

W.D Heiss

Keyword(s):

Parkinson’S Disease ◽

Gene Therapy ◽

Parkinson's Disease ◽

Molecular Imaging ◽

Disease Therapy ◽

The Future

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Translation regulation in neurodegenerative diseases: what we know about the eukaryotic elongation factor-2 kinase (eEF2K) in Alzheimer and Parkinson’s disease.

10.26226/morressier.5b31ec382afeeb001345a61c ◽

2018 ◽

Author(s):

Asad Jan

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neurodegenerative Diseases ◽

Elongation Factor ◽

Translation Regulation ◽

Elongation Factor 2 ◽

Eukaryotic Elongation Factor 2 ◽

Eukaryotic Elongation Factor

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Hunting for Familial Parkinson’s Disease Mutations in the Post Genome Era

Genes ◽

10.3390/genes12030430 ◽

2021 ◽

Vol 12 (3) ◽

pp. 430

Author(s):

Steven R. Bentley ◽

Ilaria Guella ◽

Holly E. Sherman ◽

Hannah M. Neuendorf ◽

Alex M. Sykes ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Family History ◽

Rare Variants ◽

Strong Family History ◽

Disease Mutations ◽

Whole Exome ◽

History Of ◽

Functional Consequences ◽

Multiplex Families

Parkinson’s disease (PD) is typically sporadic; however, multi-incident families provide a powerful platform to discover novel genetic forms of disease. Their identification supports deciphering molecular processes leading to disease and may inform of new therapeutic targets. The LRRK2 p.G2019S mutation causes PD in 42.5–68% of carriers by the age of 80 years. We hypothesise similarly intermediately penetrant mutations may present in multi-incident families with a generally strong family history of disease. We have analysed six multiplex families for missense variants using whole exome sequencing to find 32 rare heterozygous mutations shared amongst affected members. Included in these mutations was the KCNJ15 p.R28C variant, identified in five affected members of the same family, two elderly unaffected members of the same family, and two unrelated PD cases. Additionally, the SIPA1L1 p.R236Q variant was identified in three related affected members and an unrelated familial case. While the evidence presented here is not sufficient to assign causality to these rare variants, it does provide novel candidates for hypothesis testing in other modestly sized families with a strong family history. Future analysis will include characterisation of functional consequences and assessment of carriers in other familial cases.

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Hypoxia, Acidification and Inflammation: Partners in Crime in Parkinson’s Disease Pathogenesis?

Immuno ◽

10.3390/immuno1020006 ◽

2021 ◽

Vol 1 (2) ◽

pp. 78-90

Author(s):

Johannes Burtscher ◽

Grégoire P. Millet

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neurodegenerative Diseases ◽

Current Knowledge ◽

Cell Types ◽

Brain Cell ◽

Special Focus ◽

Molecular Alterations ◽

Research Fields

Like in other neurodegenerative diseases, protein aggregation, mitochondrial dysfunction, oxidative stress and neuroinflammation are hallmarks of Parkinson’s disease (PD). Differentiating characteristics of PD include the central role of α-synuclein in the aggregation pathology, a distinct vulnerability of the striato-nigral system with the related motor symptoms, as well as specific mitochondrial deficits. Which molecular alterations cause neurodegeneration and drive PD pathogenesis is poorly understood. Here, we summarize evidence of the involvement of three interdependent factors in PD and suggest that their interplay is likely a trigger and/or aggravator of PD-related neurodegeneration: hypoxia, acidification and inflammation. We aim to integrate the existing knowledge on the well-established role of inflammation and immunity, the emerging interest in the contribution of hypoxic insults and the rather neglected effects of brain acidification in PD pathogenesis. Their tight association as an important aspect of the disease merits detailed investigation. Consequences of related injuries are discussed in the context of aging and the interaction of different brain cell types, in particular with regard to potential consequences on the vulnerability of dopaminergic neurons in the substantia nigra. A special focus is put on the identification of current knowledge gaps and we emphasize the importance of related insights from other research fields, such as cancer research and immunometabolism, for neurodegeneration research. The highlighted interplay of hypoxia, acidification and inflammation is likely also of relevance for other neurodegenerative diseases, despite disease-specific biochemical and metabolic alterations.

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Protein Binding Partners of Dysregulated miRNAs in Parkinson’s Disease Serum

Cells ◽

10.3390/cells10040791 ◽

2021 ◽

Vol 10 (4) ◽

pp. 791

Author(s):

Wolfgang P. Ruf ◽

Axel Freischmidt ◽

Veselin Grozdanov ◽

Valerie Roth ◽

Sarah J. Brockmann ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Protein Binding ◽

Neurodegenerative Diseases ◽

Extracellular Vesicles ◽

Abundance Pattern ◽

Binding Partners ◽

Direct Binding ◽

Unsupervised Approach ◽

High Degree

Accumulating evidence suggests that microRNAs (miRNAs) are a contributing factor to neurodegenerative diseases. Although altered miRNA profiles in serum or plasma have been reported for several neurodegenerative diseases, little is known about the interaction between dysregulated miRNAs and their protein binding partners. We found significant alterations of the miRNA abundance pattern in serum and in isolated serum-derived extracellular vesicles of Parkinson’s disease (PD) patients. The differential expression of miRNA in PD patients was more robust in serum than in isolated extracellular vesicles and could separate PD patients from healthy controls in an unsupervised approach to a high degree. We identified a novel protein interaction partner for the strongly dysregulated hsa-mir-4745-5p. Our study provides further evidence for the involvement of miRNAs and HNF4a in PD. The demonstration that miRNA-protein binding might mediate the pathologic effects of HNF4a both by direct binding to it and by binding to proteins regulated by it suggests a complex role for miRNAs in pathology beyond the dysregulation of transcription.

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The Role of Salivary Biomarkers in the Early Diagnosis of Alzheimer’s Disease and Parkinson’s Disease

Diagnostics ◽

10.3390/diagnostics11020371 ◽

2021 ◽

Vol 11 (2) ◽

pp. 371

Author(s):

Patrycja Pawlik ◽

Katarzyna Błochowiak

Keyword(s):

Alzheimer’S Disease ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Parkinson's Disease ◽

Early Diagnosis ◽

Neurodegenerative Diseases ◽

Diagnostic Tool ◽

Clinical Symptoms ◽

Early Screening ◽

Salivary Biomarkers

Many neurodegenerative diseases present with progressive neuronal degeneration, which can lead to cognitive and motor impairment. Early screening and diagnosis of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are necessary to begin treatment before the onset of clinical symptoms and slow down the progression of the disease. Biomarkers have shown great potential as a diagnostic tool in the early diagnosis of many diseases, including AD and PD. However, screening for these biomarkers usually includes invasive, complex and expensive methods such as cerebrospinal fluid (CSF) sampling through a lumbar puncture. Researchers are continuously seeking to find a simpler and more reliable diagnostic tool that would be less invasive than CSF sampling. Saliva has been studied as a potential biological fluid that could be used in the diagnosis and early screening of neurodegenerative diseases. This review aims to provide an insight into the current literature concerning salivary biomarkers used in the diagnosis of AD and PD. The most commonly studied salivary biomarkers in AD are β-amyloid1-42/1-40 and TAU protein, as well as α-synuclein and protein deglycase (DJ-1) in PD. Studies continue to be conducted on this subject and researchers are attempting to find correlations between specific biomarkers and early clinical symptoms, which could be key in creating new treatments for patients before the onset of symptoms.

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Cross-platform transcriptional profiling identifies common and distinct molecular pathologies in Lewy body diseases

Acta Neuropathologica ◽

10.1007/s00401-021-02343-x ◽

2021 ◽

Author(s):

Rahel Feleke ◽

Regina H. Reynolds ◽

Amy M. Smith ◽

Bension Tilley ◽

Sarah A. Gagliano Taliun ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neurodegenerative Diseases ◽

Lewy Body ◽

Molecular Mechanisms ◽

Lewy Bodies ◽

Subsequent Development ◽

Lewy Body Dementia ◽

Anterior Cingulate ◽

Lewy Body Diseases

AbstractParkinson’s disease (PD), Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB) are three clinically, genetically and neuropathologically overlapping neurodegenerative diseases collectively known as the Lewy body diseases (LBDs). A variety of molecular mechanisms have been implicated in PD pathogenesis, but the mechanisms underlying PDD and DLB remain largely unknown, a knowledge gap that presents an impediment to the discovery of disease-modifying therapies. Transcriptomic profiling can contribute to addressing this gap, but remains limited in the LBDs. Here, we applied paired bulk-tissue and single-nucleus RNA-sequencing to anterior cingulate cortex samples derived from 28 individuals, including healthy controls, PD, PDD and DLB cases (n = 7 per group), to transcriptomically profile the LBDs. Using this approach, we (i) found transcriptional alterations in multiple cell types across the LBDs; (ii) discovered evidence for widespread dysregulation of RNA splicing, particularly in PDD and DLB; (iii) identified potential splicing factors, with links to other dementia-related neurodegenerative diseases, coordinating this dysregulation; and (iv) identified transcriptomic commonalities and distinctions between the LBDs that inform understanding of the relationships between these three clinical disorders. Together, these findings have important implications for the design of RNA-targeted therapies for these diseases and highlight a potential molecular “window” of therapeutic opportunity between the initial onset of PD and subsequent development of Lewy body dementia.

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