Protein misfolding and aggregation is observed in many amyloidogenic diseases affecting either the central nervous system or a variety of peripheral tissues. Structural and dynamic characterization of all species along the pathways from monomers to fibrils is challenging by experimental and computational means because they involve intrinsically disordered proteins in most diseases. Yet understanding how amyloid species become toxic is the challenge in developing a treatment for these diseases. Here we review what computer, in vitro, in vivo, and pharmacological experiments tell us about the accumulation and deposition of the oligomers of the (Aβ, tau), α-synuclein, IAPP, and superoxide dismutase 1 proteins, which have been the mainstream concept underlying Alzheimer's disease (AD), Parkinson's disease (PD), type II diabetes (T2D), and amyotrophic lateral sclerosis (ALS) research, respectively, for many years.

Amyloid oligomers: A joint experimental/computational perspective on Alzheimer's disease, Parkinson's disease, type II diabetes, and amyotrophic lateral sclerosis

A diagnosis of motor Parkinson's disease (PD) is preceded by a prolonged premotor phase with accumulating neuronal damage. Here we examined the temporal relation between α-synuclein (α-syn) T cell reactivity and PD. A longitudinal case study revealed that elevated α-syn-specific T cell responses were detected prior to the diagnosis of motor PD, and declined after. The relationship between T cell reactivity and early PD in two independent cohorts showed that α-syn-specific T cell responses were highest shortly after diagnosis of motor PD and then decreased. Additional analysis revealed significant association of α-syn-specific T cell responses with age and lower levodopa equivalent dose. These results confirm the presence of α-syn-reactive T cells in PD and show that they are most abundant immediately after diagnosis of motor PD. These cells may be present years before the diagnosis of motor PD, suggesting avenues of investigation into PD pathogenesis and potential early diagnosis.

/pdf/a-synuclein-specific-t-cell-reactivity-is-associated-with-1xqvcn47xx.pdf

α-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson’s disease

Immune Signaling in Neurodegeneration.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders with a global burden of approximately 6.1 million patients. Alpha-synuclein has been linked to both the sporadic and familial forms of the disease. Moreover, alpha-synuclein is present in Lewy-bodies, the neuropathological hallmark of PD, and the protein and its aggregation have been widely linked to neurotoxic pathways that ultimately lead to neurodegeneration. Such pathways include autophagy/lysosomal dysregulation, synaptic dysfunction, mitochondrial disruption, and endoplasmic reticulum (ER) and oxidative stress. Alpha-synuclein has not only been shown to alter cellular pathways but also to spread between cells, causing aggregation in host cells. Therapeutic approaches will need to address several, if not all, of these angles of alpha-synuclein toxicity. Here we review the current advances in therapeutic efforts for PD that aim to produce a disease-modifying therapy by targeting the spread, production, aggregation, and degradation of alpha-synuclein. These include: receptor blocking strategies whereby putative alpha-synuclein receptors could be blocked inhibiting alpha-synuclein spread, an alpha-synuclein reduction which will decrease the amount alpha-synuclein available for aggregation and pathway disruption, the use of small molecules in order to target alpha-synuclein aggregation, immunotherapy and the increase of alpha-synuclein degradation by increasing autophagy/lysosomal flux. The research discussed here may lead to a disease-modifying therapy that tackles disease onset and progression in the future.

/pdf/targeting-alpha-synuclein-as-a-therapy-for-parkinson-s-57w2edfm8v.pdf

Targeting Alpha-Synuclein as a Therapy for Parkinson's Disease.

α-Synuclein pathology in Parkinson’s disease and related α-synucleinopathies

https://www.zora.uzh.ch/id/eprint/170849/1/1-s2.0-S0969996118304480-main.pdf

Development of an aggregate-selective, human-derived α-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson's disease models

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Cavegn N

Author Tools

Chat about Author

Papers

Development of an aggregate-selective, human-derived α-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson's disease models