TY - JOUR
T1 - Polymorphic SERPINA3 prolongs oligomeric state of amyloid beta
AU - Akbor, Maruf Mohammad
AU - Kurosawa, Nobuyuki
AU - Nakayama, Hiroki
AU - Nakatani, Ayumi
AU - Tomobe, Koji
AU - Chiba, Yoichi
AU - Ueno, Masaki
AU - Tanaka, Masashi
AU - Nomura, Yasuyuki
AU - Isobe, Masaharu
N1 - Publisher Copyright:
© 2021 Akbor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2021/3
Y1 - 2021/3
N2 - Molecular chaperon SERPINA3 colocalizes with accumulated amyloid peptide in Alzheimer's disease (AD) patient's brain. From the QTL analysis, we narrowed down Serpina3 with two SNPs in senescence-accelerated mouse prone (SAMP) 8 strain. Our study showed SAMP8 type Serpina3 prolonged retention of oligomeric Aß 42 for longer duration (72 hr) while observing under transmission electron microscope (TEM). From Western blot results, we confirmed presence of Aß 42 oligomeric forms (trimers, tetramers) were maintained for longer duration only in the presences of SAMP8 type Serpina3. Using SH-SY5Y neuroblastoma cell line, we observed until 36 hr preincubated Aß 42 with SAMP8 type Serpina3 caused neuronal cell death compared to 12 hr preincubated Aß 42 with SAMR1 or JF1 type Serpina3 proteins. Similar results were found by extending this study to analyze the effect of polymorphism of SERPINA3 gene of the Japanese SNP database for geriatric research (JG-SNP). We observed that polymorphic SERPINA3 I308T (rs142398813) prolonged toxic oligomeric Aß 42 forms till 48 hr in comparison to the presence wild type SERPINA3 protein, resulting neuronal cell death. From this study, we first clarified pathogenic regulatory role of polymorphic SERPINA3 in neurodegeneration.
AB - Molecular chaperon SERPINA3 colocalizes with accumulated amyloid peptide in Alzheimer's disease (AD) patient's brain. From the QTL analysis, we narrowed down Serpina3 with two SNPs in senescence-accelerated mouse prone (SAMP) 8 strain. Our study showed SAMP8 type Serpina3 prolonged retention of oligomeric Aß 42 for longer duration (72 hr) while observing under transmission electron microscope (TEM). From Western blot results, we confirmed presence of Aß 42 oligomeric forms (trimers, tetramers) were maintained for longer duration only in the presences of SAMP8 type Serpina3. Using SH-SY5Y neuroblastoma cell line, we observed until 36 hr preincubated Aß 42 with SAMP8 type Serpina3 caused neuronal cell death compared to 12 hr preincubated Aß 42 with SAMR1 or JF1 type Serpina3 proteins. Similar results were found by extending this study to analyze the effect of polymorphism of SERPINA3 gene of the Japanese SNP database for geriatric research (JG-SNP). We observed that polymorphic SERPINA3 I308T (rs142398813) prolonged toxic oligomeric Aß 42 forms till 48 hr in comparison to the presence wild type SERPINA3 protein, resulting neuronal cell death. From this study, we first clarified pathogenic regulatory role of polymorphic SERPINA3 in neurodegeneration.
UR - http://www.scopus.com/inward/record.url?scp=85102482820&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0248027
DO - 10.1371/journal.pone.0248027
M3 - 学術論文
C2 - 33662018
AN - SCOPUS:85102482820
SN - 1932-6203
VL - 16
JO - PLoS ONE
JF - PLoS ONE
IS - 3 March
M1 - e0248027
ER -