Tags

Type your tag names separated by a space and hit enter

The two faces of protein misfolding: gain- and loss-of-function in neurodegenerative diseases.
EMBO J. 2008 Jan 23; 27(2):336-49.EJ

Abstract

The etiologies of neurodegenerative diseases may be diverse; however, a common pathological denominator is the formation of aberrant protein conformers and the occurrence of pathognomonic proteinaceous deposits. Different approaches coming from neuropathology, genetics, animal modeling and biophysics have established a crucial role of protein misfolding in the pathogenic process. However, there is an ongoing debate about the nature of the harmful proteinaceous species and how toxic conformers selectively damage neuronal populations. Increasing evidence indicates that soluble oligomers are associated with early pathological alterations, and strikingly, oligomeric assemblies of different disease-associated proteins may share common structural features. A major step towards the understanding of mechanisms implicated in neuronal degeneration is the identification of genes, which are responsible for familial variants of neurodegenerative diseases. Studies based on these disease-associated genes illuminated the two faces of protein misfolding in neurodegeneration: a gain of toxic function and a loss of physiological function, which can even occur in combination. Here, we summarize how these two faces of protein misfolding contribute to the pathomechanisms of Alzheimer's disease, frontotemporal lobar degeneration, Parkinson's disease and prion diseases.

Authors+Show Affiliations

Neurobiochemisty, Department of Biochemistry, Adolf-Butenandt-Institute, Ludwig-Maximilians-University, Munich, Germany. konstanze.winklhofer@med.uni-muenchen.deNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

18216876

Citation

Winklhofer, Konstanze F., et al. "The Two Faces of Protein Misfolding: Gain- and Loss-of-function in Neurodegenerative Diseases." The EMBO Journal, vol. 27, no. 2, 2008, pp. 336-49.
Winklhofer KF, Tatzelt J, Haass C. The two faces of protein misfolding: gain- and loss-of-function in neurodegenerative diseases. EMBO J. 2008;27(2):336-49.
Winklhofer, K. F., Tatzelt, J., & Haass, C. (2008). The two faces of protein misfolding: gain- and loss-of-function in neurodegenerative diseases. The EMBO Journal, 27(2), 336-49. https://doi.org/10.1038/sj.emboj.7601930
Winklhofer KF, Tatzelt J, Haass C. The Two Faces of Protein Misfolding: Gain- and Loss-of-function in Neurodegenerative Diseases. EMBO J. 2008 Jan 23;27(2):336-49. PubMed PMID: 18216876.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The two faces of protein misfolding: gain- and loss-of-function in neurodegenerative diseases. AU - Winklhofer,Konstanze F, AU - Tatzelt,Jörg, AU - Haass,Christian, PY - 2007/08/14/received PY - 2007/10/24/accepted PY - 2008/1/25/pubmed PY - 2008/4/9/medline PY - 2008/1/25/entrez SP - 336 EP - 49 JF - The EMBO journal JO - EMBO J VL - 27 IS - 2 N2 - The etiologies of neurodegenerative diseases may be diverse; however, a common pathological denominator is the formation of aberrant protein conformers and the occurrence of pathognomonic proteinaceous deposits. Different approaches coming from neuropathology, genetics, animal modeling and biophysics have established a crucial role of protein misfolding in the pathogenic process. However, there is an ongoing debate about the nature of the harmful proteinaceous species and how toxic conformers selectively damage neuronal populations. Increasing evidence indicates that soluble oligomers are associated with early pathological alterations, and strikingly, oligomeric assemblies of different disease-associated proteins may share common structural features. A major step towards the understanding of mechanisms implicated in neuronal degeneration is the identification of genes, which are responsible for familial variants of neurodegenerative diseases. Studies based on these disease-associated genes illuminated the two faces of protein misfolding in neurodegeneration: a gain of toxic function and a loss of physiological function, which can even occur in combination. Here, we summarize how these two faces of protein misfolding contribute to the pathomechanisms of Alzheimer's disease, frontotemporal lobar degeneration, Parkinson's disease and prion diseases. SN - 1460-2075 UR - https://www.unboundmedicine.com/medline/citation/18216876/The_two_faces_of_protein_misfolding:_gain__and_loss_of_function_in_neurodegenerative_diseases_ L2 - https://doi.org/10.1038/sj.emboj.7601930 DB - PRIME DP - Unbound Medicine ER -