The Role of α-Synuclein Oligomers in Parkinson’s Disease

Du, Xiaoyu; Xie, Xin; Liu, Rui‐tian

doi:10.3390/ijms21228645

Cited by 136 publications

(89 citation statements)

References 116 publications

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“…HSV-1 in not suggested to only be involved in PD, but is also suspected to participate to the pathogenesis of Alzheimer's disease (AD). Thus: (1) HSV-1 specific IgG titers and avidity are higher in AD patients compared to healthy controls [29,30]; (2) HSV-1 antibody avidity associates with AD conversion in individuals with mild cognitive impairment (MCI) [31]; (3) HSV-1 specific IgG titers positively correlate with brain grey matter volumes and cortical thinning in AD patients [30,32]; (4) in vitro and animal studies showed that HSV-1 can cause accumulation of amyloid-beta and hyperphosphorylated tau, key factors of the disease [33][34][35]; (5) an in vitro study on human neural cells showed that HSV-1 directly impairs autophagy, reducing amyloid-beta degradation [36].…”

Section: Introductionmentioning

confidence: 99%

A Possible Role for HSV-1-Specific Humoral Response and PILRA rs1859788 Polymorphism in the Pathogenesis of Parkinson’s Disease

et al. 2021

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The etiology of Parkinson’s disease (PD), a progressive nervous system disorder that affects movement, is still unknown; both genetic and environmental factor are believed to be involved in onset of the disease and its development. Herpes simplex virus type 1 (HSV-1), in particular, is suspected to have a role in PD. Paired Immunoglobulin-like type 2 receptor alpha (PILRA) is an inhibitory receptor that down-regulates inflammation and is expressed on innate immune cells. The PILRA rs1859788 polymorphism is protective against Alzheimer’s disease, even in relation with HSV-1 antibody titers, but no data are available in PD. We analyzed HSV-1 antibody titers and PILRA rs1859788 in PD (n = 51) and age-and sex-matched healthy controls (HC; n = 73). Results showed that HSV-1, but not cytomegalovirus (CMV) or human herpes virus type 6 (HHV-6) antibody titers were significantly higher in PD compared to HC (p = 0.045). The rs1859788 polymorphism was not differentially distributed between PD and HC, but the minor allele A was more frequently carried by PD (68%) compared to HC (50%) (p = 0.06). Notably, the rs1859788 minor allele A was statically more frequent in male PD (65%) compared to male HC (37%) (p = 0.036). Finally, no relation was found between HSV-1 antibody titers and PILRA genotype. Results herein suggest an involvement of HSV-1 in PD and indicate a possible interaction between PILRA gene polymorphisms and this neuropathology.

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Section: Introductionmentioning

confidence: 99%

A Possible Role for HSV-1-Specific Humoral Response and PILRA rs1859788 Polymorphism in the Pathogenesis of Parkinson’s Disease

et al. 2021

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“…Several studies have shown that α-syn oligomers are the primary cause of neurotoxicity and play a critical role in PD, similar to that of Aβ oligomers in AD [90]. Emerging evidence suggests that small soluble α-syn oligomers are the most toxic species among the forms of α-syn aggregates and that size and topological structural properties are crucial factors for oligomer-mediated toxicity, involving the interaction with either neurons or glial cells [91].…”

Section: Parkinson's Diseasementioning

confidence: 99%

Green Tea Epigallocatechin-3-gallate (EGCG) Targeting Protein Misfolding in Drug Discovery for Neurodegenerative Diseases

2021

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The potential to treat neurodegenerative diseases (NDs) of the major bioactive compound of green tea, epigallocatechin-3-gallate (EGCG), is well documented. Numerous findings now suggest that EGCG targets protein misfolding and aggregation, a common cause and pathological mechanism in many NDs. Several studies have shown that EGCG interacts with misfolded proteins such as amyloid beta-peptide (Aβ), linked to Alzheimer’s disease (AD), and α-synuclein, linked to Parkinson’s disease (PD). To date, NDs constitute a serious public health problem, causing a financial burden for health care systems worldwide. Although current treatments provide symptomatic relief, they do not stop or even slow the progression of these devastating disorders. Therefore, there is an urgent need to develop effective drugs for these incurable ailments. It is expected that targeting protein misfolding can serve as a therapeutic strategy for many NDs since protein misfolding is a common cause of neurodegeneration. In this context, EGCG may offer great potential opportunities in drug discovery for NDs. Therefore, this review critically discusses the role of EGCG in NDs drug discovery and provides updated information on the scientific evidence that EGCG can potentially be used to treat many of these fatal brain disorders.

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“…DS is caused by heterozygous loss-of-function mutations in the SCN1A gene, which encodes the pore-forming alpha subunit of the voltage-gated sodium channel Nav1.1. Majority of DS mutations lead to insufficient levels of SCN1A protein in inhibitory neurons where it is preferentially expressed ( XY. Du et al, 2020 ).…”

Section: Nbts In Orphan Neurological Disordersmentioning

confidence: 99%

Nucleic Acid–Based Therapeutics in Orphan Neurological Disorders: Recent Developments

Khorkova

Hsiao

Wahlestedt

2021

Front. Mol. Biosci.

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The possibility of rational design and the resulting faster and more cost-efficient development cycles of nucleic acid–based therapeutics (NBTs), such as antisense oligonucleotides, siRNAs, and gene therapy vectors, have fueled increased activity in developing therapies for orphan diseases. Despite the difficulty of delivering NBTs beyond the blood–brain barrier, neurological diseases are significantly represented among the first targets for NBTs. As orphan disease NBTs are now entering the clinical stage, substantial efforts are required to develop the scientific background and infrastructure for NBT design and mechanistic studies, genetic testing, understanding natural history of orphan disorders, data sharing, NBT manufacturing, and regulatory support. The outcomes of these efforts will also benefit patients with “common” diseases by improving diagnostics, developing the widely applicable NBT technology platforms, and promoting deeper understanding of biological mechanisms that underlie disease pathogenesis. Furthermore, with successes in genetic research, a growing proportion of “common” disease cases can now be attributed to mutations in particular genes, essentially extending the orphan disease field. Together, the developments occurring in orphan diseases are building the foundation for the future of personalized medicine. In this review, we will focus on recent achievements in developing therapies for orphan neurological disorders.

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The Role of α-Synuclein Oligomers in Parkinson’s Disease

Cited by 136 publications

References 116 publications

A Possible Role for HSV-1-Specific Humoral Response and PILRA rs1859788 Polymorphism in the Pathogenesis of Parkinson’s Disease

A Possible Role for HSV-1-Specific Humoral Response and PILRA rs1859788 Polymorphism in the Pathogenesis of Parkinson’s Disease

Green Tea Epigallocatechin-3-gallate (EGCG) Targeting Protein Misfolding in Drug Discovery for Neurodegenerative Diseases

Nucleic Acid–Based Therapeutics in Orphan Neurological Disorders: Recent Developments

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