Lack of association between cathepsin D C224T polymorphism and Alzheimer’s disease risk: an update meta-analysis

Mo, Cuiju; Peng, Qiliu; Sui, Jingzhe; Wang, Jian; Deng, Yan; Xie, Li; Li, Taijie; He, Yu; Xue, Qiang; Li, Shan

doi:10.1186/1471-2377-14-13

Cited by 8 publications

(5 citation statements)

References 45 publications

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“…Meta-analysis is a valuable tool to identify disease genes [65] leading us to conduct the present study. Our results indicate that the Taq1A homozygote model is associated with schizophrenia susceptibility, as well as the -141C Ins/Del allele frequency and recessive model in all populations studied.…”

Section: Discussionmentioning

confidence: 99%

The -141C Ins/Del and Taq1A polymorphism in the dopamine D2 receptor gene may confer susceptibility to schizophrenia in Asian populations

Wang¹,

Liu

Xin

et al. 2016

Journal of Clinical Neuroscience

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Section: Discussionmentioning

confidence: 99%

The -141C Ins/Del and Taq1A polymorphism in the dopamine D2 receptor gene may confer susceptibility to schizophrenia in Asian populations

Wang¹,

Liu

Xin

et al. 2016

Journal of Clinical Neuroscience

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“…Two meta-analyses on the influence of CTSD mutation rs17571 on AD yielded contrary results ( Schuur et al, 2011 ; Mo et al, 2014 ). Similar discrepancy is also reported for another CTSD mutation (Ala224Val) ( Ntais et al, 2004 ; Paz-Y-Miño et al, 2015 ).…”

Section: Biological Mechanisms Linking Autophagy and Admentioning

confidence: 97%

Autophagy and Alzheimer’s Disease: From Molecular Mechanisms to Therapeutic Implications

Uddin

Stachowiak

Mamun

et al. 2018

Front. Aging Neurosci.

331

247

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Alzheimer’s disease (AD) is the most common cause of progressive dementia in the elderly. It is characterized by a progressive and irreversible loss of cognitive abilities and formation of senile plaques, composed mainly of amyloid β (Aβ), and neurofibrillary tangles (NFTs), composed of tau protein, in the hippocampus and cortex of afflicted humans. In brains of AD patients the metabolism of Aβ is dysregulated, which leads to the accumulation and aggregation of Aβ. Metabolism of Aβ and tau proteins is crucially influenced by autophagy. Autophagy is a lysosome-dependent, homeostatic process, in which organelles and proteins are degraded and recycled into energy. Thus, dysfunction of autophagy is suggested to lead to the accretion of noxious proteins in the AD brain. In the present review, we describe the process of autophagy and its importance in AD. Additionally, we discuss mechanisms and genes linking autophagy and AD, i.e., the mTOR pathway, neuroinflammation, endocannabinoid system, ATG7, BCL2, BECN1, CDK5, CLU, CTSD, FOXO1, GFAP, ITPR1, MAPT, PSEN1, SNCA, UBQLN1, and UCHL1. We also present pharmacological agents acting via modulation of autophagy that may show promise in AD therapy. This review updates our knowledge on autophagy mechanisms proposing novel therapeutic targets for the treatment of AD.

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“…Indeed, several studies reported the association between the rs17571 (C→T) polymorphism and the occurrence of sporadic, late‐onset AD . However, other studies did not confirm this observation, and two recent meta‐analyses again led to contradictory results, one confirming and the other excluding a significant correlation between the expression of A38V cathepsin D and the risk of developing sporadic AD. That said, the studies consistently demonstrate that the expression of the A38V CTSD allele acts in concert with the APOE4 allele in promoting the deposition of Aβ plaques in the brain …”

Section: Introductionmentioning

confidence: 99%

The Role of Cathepsin D in the Pathogenesis of Human Neurodegenerative Disorders

Vidoni

Follo

Savino

et al. 2016

Medicinal Research Reviews

128

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In familial neurodegenerative disorders, protein aggregates form continuously because of genetic mutations that drive the synthesis of truncated or unfolded proteins. The oxidative stress imposed by neurotransmitters and environmental neurotoxins constitutes an additional threat to the folding of the proteins and the integrity of organelle membranes in neurons. Failure in degrading such altered materials compromises the function of neurons and eventually leads to neurodegeneration. The lysosomal proteolytic enzyme Cathepsin D is the only aspartic-type protease ubiquitously expressed in all the cells of the human body, and it is expressed at high level in the brain. In general, cathepsin D mediated proteolysis is essential to neuronal cell homeostasis through the degradation of unfolded or oxidized protein aggregates delivered to lysosomes via autophagy or endocytosis. More specifically, many altered neuronal proteins that hallmark neurodegenerative diseases (e.g., the amyloid precursor, α-synuclein, and huntingtin) are physiologic substrates of cathepsin D and would abnormally accumulate if not efficiently degraded by this enzyme. Furthermore, experimental evidence indicates that cathepsin D activity is linked to the metabolism of cholesterol and of glycosaminoglycans, which accounts for its involvement in neuronal plasticity. This review focuses on the unique role of cathepsin D mediated proteolysis in the pathogenesis of human neurodegenerative diseases.

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Lack of association between cathepsin D C224T polymorphism and Alzheimer’s disease risk: an update meta-analysis

Cited by 8 publications

References 45 publications

The -141C Ins/Del and Taq1A polymorphism in the dopamine D2 receptor gene may confer susceptibility to schizophrenia in Asian populations

The -141C Ins/Del and Taq1A polymorphism in the dopamine D2 receptor gene may confer susceptibility to schizophrenia in Asian populations

Autophagy and Alzheimer’s Disease: From Molecular Mechanisms to Therapeutic Implications

The Role of Cathepsin D in the Pathogenesis of Human Neurodegenerative Disorders

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