TY - JOUR
T1 - Protein homeostasis of a metastable subproteome associated with Alzheimer's disease
AU - Kundra, Rishika
AU - Ciryam, Prajwal
AU - Morimoto, Richard I.
AU - Dobson, Christopher M.
AU - Vendruscolo, Michele
PY - 2017/7/11
Y1 - 2017/7/11
N2 - Alzheimer's disease is the most common cause of dementia. A hallmark of this disease is the presence of aberrant deposits containing by the Aβ peptide (amyloid plaques) and the tau protein (neurofibrillary tangles) in the brains of affected individuals. Increasing evidence suggests that the formation of these deposits is closely associated with the age-related dysregulation of a large set of highly expressed and aggregation-prone proteins, which make up a metastable subproteome. To understand in more detail the origins of such dysregulation, we identify specific components of the protein homeostasis system associated with these metastable proteins by using a gene coexpression analysis. Our results reveal the particular importance of the protein trafficking and clearance mechanisms, including specific branches of the endosomal-lysosomal and ubiquitin-proteasome systems, in maintaining the homeostasis of the metastable subproteome associated with Alzheimer's disease.
AB - Alzheimer's disease is the most common cause of dementia. A hallmark of this disease is the presence of aberrant deposits containing by the Aβ peptide (amyloid plaques) and the tau protein (neurofibrillary tangles) in the brains of affected individuals. Increasing evidence suggests that the formation of these deposits is closely associated with the age-related dysregulation of a large set of highly expressed and aggregation-prone proteins, which make up a metastable subproteome. To understand in more detail the origins of such dysregulation, we identify specific components of the protein homeostasis system associated with these metastable proteins by using a gene coexpression analysis. Our results reveal the particular importance of the protein trafficking and clearance mechanisms, including specific branches of the endosomal-lysosomal and ubiquitin-proteasome systems, in maintaining the homeostasis of the metastable subproteome associated with Alzheimer's disease.
KW - Alzheimer's disease
KW - Protein aggregation
KW - Protein homeostasis
KW - Supersaturation
UR - http://www.scopus.com/inward/record.url?scp=85023196179&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85023196179&partnerID=8YFLogxK
U2 - 10.1073/pnas.1618417114
DO - 10.1073/pnas.1618417114
M3 - Article
C2 - 28652376
AN - SCOPUS:85023196179
SN - 0027-8424
VL - 114
SP - E5703-E5711
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 28
ER -