Genetic polymorphisms of lipid metabolism gene SAR1 homolog B and the risk of Alzheimer's disease and vascular dementia

Chen, Jen‐Hau; Hsieh, Chia-Sheng; Huang, Yi‐Ling; Chen, Yen‐Ching; Chen, Ta‐Fu; Sun, Yu; Wen, Li-Li; Yip, Ping-Keung; Chu, Yi-Min

doi:10.1016/j.jfma.2015.01.008

Cited by 8 publications

(6 citation statements)

References 52 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accumulating evidence has demonstrated that genes encoding certain endocytosis-related proteins are the targets of chromosomal rearrangement in human hematopoietic malignancies, and abnormal expression or mutations of these proteins have been reported in human cancer, suggesting a potential link between endocytosis proteins and cancer (36). SAR1B is a GTPase that serves a key role in the exportation of proteins from the ER to the Golgi apparatus by recruiting β-COP to the ER and promoting vesicular transport (10,37,38). Considering the essential function of lipids in cancer, it is possible that SAR1B may affect the molecular mechanisms involved in cell proliferation or apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of SAR1B suppresses proliferation and induces apoptosis of RKO colorectal cancer cells

Zhou

Chen

et al. 2020

Oncol Lett

View full text Add to dashboard Cite

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. SAR1 gene homolog B (SAR1B) is a GTPase that has been reported to have a central role in the regulation of lipid homeostasis and is associated with numerous diseases. However, its role in cancer, particularly in CRC, remains unclear. The present study revealed that SAR1B was overexpressed in CRC samples and this was associated with shorter overall survival time in patients with CRC. Colony formation, cell proliferation and flow cytometry assays were conducted to evaluate the functions of SAR1B in CRC. It was reported that SAR1B may be associated with tumorigenesis of CRC. Knockdown of SAR1B suppressed cell proliferation and induced significant apoptosis of RKO cells. Furthermore, microarray analysis was performed to identify the potential targets of SAR1B in CRC. Bioinformatics analysis revealed that SAR1B was significantly involved in regulating 'TGF-β signaling', 'paxillin signaling', 'cell cycle regulation by BTG family proteins' and 'IGF-1 signaling'. These results suggested that SAR1B may be considered a potential prognostic biomarker and therapeutic target for CRC.

show abstract

Section: Discussionmentioning

confidence: 99%

Knockdown of SAR1B suppresses proliferation and induces apoptosis of RKO colorectal cancer cells

Zhou

Chen

et al. 2020

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…CADASIL and HCHWA are the only known high‐penetrance genetic causes for small vessel VaD. Existing evidence thus far support the notion that most small vessel VaD is a product of genetic predisposition and environmental interaction. Hypertension is one such important environmental risk factor.…”

Section: Genetic Factorsmentioning

confidence: 99%

Genetic and environmental factors in vascular dementia: an update of blood brain barrier dysfunction

Srinivasan

Braidy

Chan

et al. 2016

Clin Exp Pharma Physio

View full text Add to dashboard Cite

SUMMARYVascular dementia (VaD) describes a combination of both cognitive and behavioural manifestations associated with variable brain lesions of vascular origin. While vascular risk factors have been implicated in VaD, the relationship is most evident when the factors are considered together and not individually. This review will examine the significance of the integrity of blood brain barrier (BBB) tight junction (TJ) proteins -occludin and claudins in the pathophysiology of VaD. Specifically, some of the genetic contributors to VaD, namely those responsible for the integrity of the BBB, will be reviewed in detail. Moreover, environmental factors will be considered in conjunction with these genes to examine how the interaction of environmental and genetic factors contributes to one's susceptibility to VaD.

show abstract

“…Despite years of intensive research, the link between hyperlipidemia and AD has yet to be established, although it has previously been suggested that genes regulating lipid metabolism may also be important in AD (11). Proprotein convertase subtilisin/kexin type 9 (PCSK9) encodes a protein formerly termed neuronal apoptosis-regulated convertase-1, a proprotein convertase belonging to the subtilase subfamily (12).…”

Section: Introductionmentioning

confidence: 99%

Hyperlipidemia-induced apoptosis of hippocampal neurons in apoE(−/−) mice may be associated with increased PCSK9 expression

Zhao¹,

Wu²,

Peng³

et al. 2016

Molecular Medicine Reports

View full text Add to dashboard Cite

Hyperlipidemia is a risk factor for Alzheimer's disease (AD) and other neurodegenerative diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a lipid regulatory gene involved in cell apoptosis. However, the function and mechanism of PCSK9 in neuronal apoptosis following hyperlipidemia remains to be elucidated. The present study established a hyperlipidemic mouse model by feeding a high-fat diet (HFD) to 6-week-old apoE(−/−) mice. Plasma lipid levels, hippocampal lipid accumulation, hippocampal histology, and hippocampal neuronal apoptosis were all monitored for changes. The expression levels of PCSK9, β-secretase 1 (BACE1), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and caspase-3 in hippocampal CA3 and CA1 neurons were also measured. Results demonstrated that a HFD increased the lipid accumulation in the CA3 hippocampus and the levels of plasma lipids, including triglycerides, total cholesterol, low-density lipoprotein, and high-density lipoprotein. In addition, CA3 neurons in the HFD group indicated apparent injuries and increased neuronal apoptosis, which are associated with the expression of Bcl-2, Bax, and caspase-3. A HFD also increased the expression levels of PCSK9 and BACE1. BACE1 promotes cleavage of amyloid precursor proteins to generate β-amyloid peptide (Aβ), which induces neuronal apoptosis. Protein levels of Aβ are associated with the observation of amyloid plaques in the hippocampus of the HFD group. The results suggest that hyperlipidemia regulates neuronal apoptosis by increasing PCSK9 and BACE1 expression. Overall, the current study may elucidate the role of lipid metabolism disorder in AD pathogenesis.

show abstract

Genetic polymorphisms of lipid metabolism gene SAR1 homolog B and the risk of Alzheimer's disease and vascular dementia

Abstract: SAR1B polymorphisms were associated with AD risk; results were not significant after correction for multiple tests. Simultaneous screening using SAR1B rs11948613 and ApoE ε4 status offered a better sensitivity for AD screening.

Cited by 8 publications

References 52 publications

Knockdown of SAR1B suppresses proliferation and induces apoptosis of RKO colorectal cancer cells

Knockdown of SAR1B suppresses proliferation and induces apoptosis of RKO colorectal cancer cells

Genetic and environmental factors in vascular dementia: an update of blood brain barrier dysfunction

Hyperlipidemia-induced apoptosis of hippocampal neurons in apoE(−/−) mice may be associated with increased PCSK9 expression

Contact Info

Product

Resources

About