TY  - JOUR
AU  - Outeiro, Tiago Fleming
AU  - Höglinger, Günter
AU  - Lang, Anthony E
AU  - Vieira, Tuane C R G
TI  - Protein misfolding: understanding biology to classify and treat synucleinopathies.
JO  - Journal of neural transmission
VL  - 132
IS  - 11
SN  - 0375-9245
CY  - Wien [u.a.]
PB  - Springer
M1  - DZNE-2025-01294
SP  - 1645 - 1654
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Synucleinopathies: metabolism
KW  - Synucleinopathies: classification
KW  - Synucleinopathies: therapy
KW  - Protein Folding
KW  - Proteostasis Deficiencies: metabolism
KW  - Proteostasis Deficiencies: therapy
KW  - Animals
KW  - Alpha-synuclein (Other)
KW  - Biomarkers (Other)
KW  - Disease classification (Other)
KW  - Neurodegeneration (Other)
KW  - Parkinson’s disease (Other)
KW  - Protein aggregation (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39932548
DO  - DOI:10.1007/s00702-025-02889-0
UR  - https://pub.dzne.de/record/282333
ER  -