Journal Article (Review Article)

DZNE-2025-01294

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Protein misfolding: understanding biology to classify and treat synucleinopathies.

Outeiro, T. F. (First author)DZNE* ; Höglinger, G.DZNE* ; Lang, A. E. ; Vieira, T. C. R. G.

2025
Springer Wien [u.a.]

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Please use a persistent id in citations: doi:10.1007/s00702-025-02889-0

Abstract: Protein misfolding and aggregation is a major pathological hallmark in a variety of human conditions, including cancer, diabetes, and neurodegeneration. However, we still do not fully understand the role of protein accumulation in disease. Interestingly, recent breakthroughs in artificial intelligence (AI) are having a tremendous impact on our ability to predict three-dimensional protein structures and understand the molecular rules governing protein folding/misfolding. This progress will enable us to understand how intrinsic and extrinsic factors trigger protein misfolding, thereby changing protein function. These changes, in some cases, are related to normal biological responses and, in other cases, associated with pathological alterations, such as those found in many neurodegenerative disorders. Here, we provide a brief historical perspective of how findings in the field of prion diseases and prion biology have enabled tremendous advances that are now forming the basis for our understanding of disease processes and discuss how this knowledge is now emerging as central for our ability to classify, diagnose, and treat devastating neurodegenerative disorders such as Parkinson's and Alzheimer's diseases.

Keyword(s): Humans (MeSH) ; Synucleinopathies: metabolism (MeSH) ; Synucleinopathies: classification (MeSH) ; Synucleinopathies: therapy (MeSH) ; Protein Folding (MeSH) ; Proteostasis Deficiencies: metabolism (MeSH) ; Proteostasis Deficiencies: therapy (MeSH) ; Animals (MeSH) ; Alpha-synuclein ; Biomarkers ; Disease classification ; Neurodegeneration ; Parkinson’s disease ; Protein aggregation

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Contributing Institute(s):

1. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer)
2. Clinical Research (Munich) (Clinical Research (Munich))

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)
2. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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