Tags

Type your tag names separated by a space and hit enter

Protein misfolding in the late-onset neurodegenerative diseases: common themes and the unique case of amyotrophic lateral sclerosis.
Proteins. 2013 Aug; 81(8):1285-303.P

Abstract

Enormous strides have been made in the last 100 years to extend human life expectancy and to combat the major infectious diseases. Today, the major challenges for medical science are age-related diseases, including cancer, heart disease, lung disease, renal disease, and late-onset neurodegenerative disease. Of these, only the neurodegenerative diseases represent a class of disease so poorly understood that no general strategies for prevention or treatment exist. These diseases, which include Alzheimer's disease, Parkinson's disease, Huntington's disease, the transmissible spongiform encephalopathies, and amyotrophic lateral sclerosis (ALS), are generally fatal and incurable. The first section of this review summarizes the diversity and common features of the late-onset neurodegenerative diseases, with a particular focus on protein misfolding and aggregation-a recurring theme in the molecular pathology. The second section focuses on the particular case of ALS, a late-onset neurodegenerative disease characterized by the death of central nervous system motor neurons, leading to paralysis and patient death. Of the 10% of ALS cases that show familial inheritance (familial ALS), the largest subset is caused by mutations in the SOD1 gene, encoding the Cu, Zn superoxide dismutase (SOD1). The unusual kinetic stability of SOD1 has provided a unique opportunity for detailed structural characterization of conformational states potentially involved in SOD1-associated ALS. This review discusses past studies exploring the stability, folding, and misfolding behavior of SOD1, as well as the therapeutic possibilities of using detailed knowledge of misfolding pathways to target the molecular mechanisms underlying ALS and other neurodegenerative diseases.

Authors+Show Affiliations

Department of Biochemistry, University of Washington, Seattle, Washington, USA.No affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

23508986

Citation

Mulligan, Vikram Khipple, and Avijit Chakrabartty. "Protein Misfolding in the Late-onset Neurodegenerative Diseases: Common Themes and the Unique Case of Amyotrophic Lateral Sclerosis." Proteins, vol. 81, no. 8, 2013, pp. 1285-303.
Mulligan VK, Chakrabartty A. Protein misfolding in the late-onset neurodegenerative diseases: common themes and the unique case of amyotrophic lateral sclerosis. Proteins. 2013;81(8):1285-303.
Mulligan, V. K., & Chakrabartty, A. (2013). Protein misfolding in the late-onset neurodegenerative diseases: common themes and the unique case of amyotrophic lateral sclerosis. Proteins, 81(8), 1285-303. https://doi.org/10.1002/prot.24285
Mulligan VK, Chakrabartty A. Protein Misfolding in the Late-onset Neurodegenerative Diseases: Common Themes and the Unique Case of Amyotrophic Lateral Sclerosis. Proteins. 2013;81(8):1285-303. PubMed PMID: 23508986.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protein misfolding in the late-onset neurodegenerative diseases: common themes and the unique case of amyotrophic lateral sclerosis. AU - Mulligan,Vikram Khipple, AU - Chakrabartty,Avijit, Y1 - 2013/07/02/ PY - 2012/11/01/received PY - 2013/02/27/revised PY - 2013/02/28/accepted PY - 2013/3/20/entrez PY - 2013/3/20/pubmed PY - 2014/2/6/medline KW - Alzheimer's disease KW - Huntington's disease KW - Parkinson's disease KW - ageing KW - amyloid KW - folding kinetics KW - folding pathways KW - prion disease KW - protein aggregation KW - senescence SP - 1285 EP - 303 JF - Proteins JO - Proteins VL - 81 IS - 8 N2 - Enormous strides have been made in the last 100 years to extend human life expectancy and to combat the major infectious diseases. Today, the major challenges for medical science are age-related diseases, including cancer, heart disease, lung disease, renal disease, and late-onset neurodegenerative disease. Of these, only the neurodegenerative diseases represent a class of disease so poorly understood that no general strategies for prevention or treatment exist. These diseases, which include Alzheimer's disease, Parkinson's disease, Huntington's disease, the transmissible spongiform encephalopathies, and amyotrophic lateral sclerosis (ALS), are generally fatal and incurable. The first section of this review summarizes the diversity and common features of the late-onset neurodegenerative diseases, with a particular focus on protein misfolding and aggregation-a recurring theme in the molecular pathology. The second section focuses on the particular case of ALS, a late-onset neurodegenerative disease characterized by the death of central nervous system motor neurons, leading to paralysis and patient death. Of the 10% of ALS cases that show familial inheritance (familial ALS), the largest subset is caused by mutations in the SOD1 gene, encoding the Cu, Zn superoxide dismutase (SOD1). The unusual kinetic stability of SOD1 has provided a unique opportunity for detailed structural characterization of conformational states potentially involved in SOD1-associated ALS. This review discusses past studies exploring the stability, folding, and misfolding behavior of SOD1, as well as the therapeutic possibilities of using detailed knowledge of misfolding pathways to target the molecular mechanisms underlying ALS and other neurodegenerative diseases. SN - 1097-0134 UR - https://www.unboundmedicine.com/medline/citation/23508986/Protein_misfolding_in_the_late_onset_neurodegenerative_diseases:_common_themes_and_the_unique_case_of_amyotrophic_lateral_sclerosis_ DB - PRIME DP - Unbound Medicine ER -