Implications of the serine protease HtrA1 in amyloid precursor protein processing.
The defining features of the widely conserved HtrA (high temperature requirement) family of serine proteases are the combination of a catalytic protease domain with one or more C-terminal PDZ domains and reversible zymogen activation. Even though HtrAs have previously been implicated in protein quality control and various diseases, including cancer, arthritis, and neuromuscular disorder, the biology of the human family members is not well understood. Our data suggest that HtrA1 is directly involved in the beta-amyloid pathway as it degrades various fragments of amyloid precursor protein while an HtrA1 inhibitor causes accumulation of Abeta in astrocyte cell culture supernatants. Furthermore, HtrA1 colocalizes with beta-amyloid deposits in human brain samples. Potential implications in Alzheimer's disease are discussed.
Grau
Sandra
S
School of Biosciences, Cardiff University, Cardiff CF10 3US, United Kingdom.
Baldi
Alfonso
A
Bussani
Rossana
R
Tian
Xiaodan
X
Stefanescu
Raluca
R
Przybylski
Michael
M
Richards
Peter
P
Jones
Simon A
SA
Shridhar
Viji
V
Clausen
Tim
T
Ehrmann
Michael
M
D000368:Aged; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001344:Autopsy; D001921:Brain / Q000201:enzymology; D017124:Conserved Sequence; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D011994:Recombinant Proteins; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases