Редактирование: BIN1

Myc box-dependent-interacting protein 1 (Amphiphysin II) (Amphiphysin-like protein) (Box-dependent myc-interacting protein 1) (Bridging integrator 1) [AMPHL]

==Publications==

{{medline-entry
|title=Amphiphysin 2 modulation rescues myotubular myopathy and prevents focal adhesion defects in mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30894500
|abstract=Centronuclear myopathies (CNMs) are severe diseases characterized by muscle weakness and myofiber atrophy. Currently, there are no approved treatments for these disorders. Mutations in the phosphoinositide 3-phosphatase myotubularin ([[MTM1]]) are responsible for X-linked CNM (XLCNM), also called myotubular myopathy, whereas mutations in the membrane remodeling Bin/amphiphysin/Rvs protein amphiphysin 2 [bridging integrator 1 ([[BIN1]])] are responsible for an autosomal form of the disease. Here, we investigated the functional relationship between [[MTM1]] and [[BIN1]] in healthy skeletal muscle and in the physiopathology of CNM. Genetic overexpression of human [[BIN1]] efficiently rescued the muscle weakness and life span in a mouse model of XLCNM. Exogenous human [[BIN1]] expression with adeno-associated virus after birth also prevented the progression of the disease, suggesting that human [[BIN1]] overexpression can compensate for the lack of [[MTM1]] expression in this mouse model. Our results showed that [[MTM1]] controls cell adhesion and integrin localization in mammalian muscle. Alterations in this pathway in [i]Mtm1[/i]   mice were associated with defects in myofiber shape and size. [[BIN1]] expression rescued integrin and laminin alterations and restored myofiber integrity, supporting the idea that [[MTM1]] and [[BIN1]] are functionally linked and necessary for focal adhesions in skeletal muscle. The results suggest that [[BIN1]] modulation might be an effective strategy for treating XLCNM.
|mesh-terms=* Adaptor Proteins, Signal Transducing
* Animals
* Animals, Newborn
* Focal Adhesions
* Humans
* Integrin beta1
* Longevity
* Male
* Mice, Transgenic
* Muscle Strength
* Muscles
* Myopathies, Structural, Congenital
* Nerve Tissue Proteins
* Nuclear Proteins
* Protein Tyrosine Phosphatases, Non-Receptor
* Tumor Suppressor Proteins

|full-text-url=https://sci-hub.do/10.1126/scitranslmed.aav1866
}}
{{medline-entry
|title=Recent studies on cellular and molecular mechanisms in Alzheimer's disease: focus on epigenetic factors and histone deacetylase.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29397389
|abstract=Alzheimer's disease (AD) is one of the most common neurodegenerative disorders mainly affecting elderly people. It is characterized by progressive loss of memory and cognitive function. More than 95% of AD cases are related to sporadic or late-onset AD (LOAD). The etiology of LOAD is still unclear. It has been reported that environmental factors and epigenetic alterations play a significant role in AD pathogenesis. Furthermore, recently, genome-wide association studies (GWAS) identified 10 novel risk genes: [[ABCA7]], [[APOE]], [[BIN1]], [[CD2AP]], [[CD33]], [[CLU]], [[CR1]], [[MS4A6A]], [[MS4A4E]], and [[PICALM]], which play an important role for LOAD. In this review, the therapeutic approaches of AD by epigenetic modifications have been discussed. Nowadays, HDAC inhibitors have clinically proven its activity for epigenetic modifications. Furthermore, we try to establish the relationship between HDAC inhibitors and above mentioned LOAD risk genes. Finally, we are hoping that this review may open new area of research for AD treatment.
|mesh-terms=* Aging
* Alzheimer Disease
* Animals
* Cognition Disorders
* Epigenesis, Genetic
* Genetic Predisposition to Disease
* Genome-Wide Association Study
* Histone Deacetylase Inhibitors
* Histone Deacetylases
* Humans
|keywords=* Alzheimer’s disease
* GWAS
* HDAC inhibitors
* LOAD
* epigenetic modification
|full-text-url=https://sci-hub.do/10.1515/revneuro-2017-0049
}}
{{medline-entry
|title=Association and interaction effects of Alzheimer's disease-associated genes and lifestyle on cognitive aging in older adults in a Taiwanese population.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28199971
|abstract=Genome-wide association studies and meta-analyses implicated that increased risk of developing Alzheimer's diseases (AD) has been associated with the [[ABCA7]], [[APOE]], [[BIN1]], [[CASS4]], [[CD2AP]], [[CD33]], [[CELF1]], [[CLU]], [[CR1]], [[DSG2]], [[EPHA1]], [[FERMT2]], [[HLA-DRB1]], [[HLA-DRB4]], [[INPP5D]], [[MEF2C]], [[MS4A4A]], [[MS4A4E]], [[MS4A6E]], [[NME8]], [[PICALM]], [[PLD3]], [[PTK2B]], [[RIN3]], [[SLC24A4]], [[SORL1]], and [[ZCWPW1]] genes. In this study, we assessed whether single nucleotide polymorphisms (SNPs) within these 27 AD-associatedgenes are linked with cognitive aging independently and/or through complex interactions in an older Taiwanese population. We also analyzed the interactions between lifestyle and these genes in influencing cognitive aging. A total of 634 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed. Mini-Mental State Examination (MMSE) scores were performed for all subjects to evaluate cognitive functions. Out of the 588 SNPs tested in this study, only the association between [[CASS4]]-rs911159 and cognitive aging persisted significantly (P = 2.2 x 10-5) after Bonferroni correction. Our data also showed a nominal association of cognitive aging with the SNPs in six more key AD-associated genes, including [[EPHA1]]-rs10952552, [[FERMT2]]-rs4901317, [[MEF2C]]-rs9293506, [[PLD3]]-rs11672825, [[RIN3]]-rs1885747, and [[SLC24A4]]-rs67063100 (P = 0.0018~0.0097). Additionally, we found the interactions among [[CASS4]]-rs911159, EPHA-rs10952552, [[FERMT2]]-rs4901317, [[MEF2C]]-rs9293506, or [[SLC24A4]]-rs67063100 on cognitive aging (P = 0.004~0.035). Moreover, our analysis suggested the interactions of [[SLC24A4]]-rs67063100 or [[MEF2C]]-rs9293506 with lifestyle such as alcohol consumption, smoking status, physical activity, or social support on cognitive aging (P = 0.008~0.041). Our study indicates that the AD-associated genes may contribute to the risk of cognitive aging independently as well as through gene-gene and gene-lifestyle interactions.
|mesh-terms=* Age Factors
* Aged
* Alleles
* Alzheimer Disease
* Cognitive Aging
* Epistasis, Genetic
* Female
* Gene-Environment Interaction
* Genetic Association Studies
* Genetic Predisposition to Disease
* Humans
* Life Style
* Male
* Middle Aged
* Polymorphism, Single Nucleotide
* Risk Factors
* Taiwan
|keywords=* Alzheimer’s diseases
* Gerotarget
* Mini-Mental State Examination
* cognitive aging
* gene-gene and gene-lifestyle interactions
* single nucleotide polymorphisms
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421828
}}
{{medline-entry
|title=Dopamine Receptor Genes Modulate Associative Memory in Old Age.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27647283
|abstract=Previous research shows that associative memory declines more than item memory in aging. Although the underlying mechanisms of this selective impairment remain poorly understood, animal and human data suggest that dopaminergic modulation may be particularly relevant for associative binding. We investigated the influence of dopamine (DA) receptor genes on item and associative memory in a population-based sample of older adults (n = 525, aged 60 years), assessed with a face-scene item associative memory task. The effects of single-nucleotide polymorphisms of DA D1 (DRD1; rs4532), D2 ([[DRD2]]/ANKK1/Taq1A; rs1800497), and D3 ([[DRD3]]/Ser9Gly; rs6280) receptor genes were examined and combined into a single genetic score. Individuals carrying more beneficial alleles, presumably associated with higher DA receptor efficacy (DRD1 C allele; [[DRD2]] A2 allele; [[DRD3]] T allele), performed better on associative memory than persons with less beneficial genotypes. There were no effects of these genes on item memory or other cognitive measures, such as working memory, executive functioning, fluency, and perceptual speed, indicating a selective association between DA genes and associative memory. By contrast, genetic risk for Alzheimer disease (AD) was associated with worse item and associative memory, indicating adverse effects of [[APOE]] ε4 and a genetic risk score for AD (PICALM, [[BIN1]], CLU) on episodic memory in general. Taken together, our results suggest that DA may be particularly important for associative memory, whereas AD-related genetic variations may influence overall episodic memory in older adults without dementia.
|mesh-terms=* Aging
* Alzheimer Disease
* Apolipoproteins E
* Association
* Cohort Studies
* Female
* Genotyping Techniques
* Humans
* Male
* Memory
* Middle Aged
* Neuropsychological Tests
* Polymorphism, Single Nucleotide
* Receptors, Dopamine

|full-text-url=https://sci-hub.do/10.1162/jocn_a_01048
}}
{{medline-entry
|title=Gene-based aggregate SNP associations between candidate AD genes and cognitive decline.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27005436
|abstract=Single nucleotide polymorphisms (SNPs) in and near [[ABCA7]], [[BIN1]], [[CASS4]], [[CD2AP]], [[CD33]], [[CELF1]], [[CLU]], complement receptor 1 ([[CR1]]), [[EPHA1]], [[EXOC3L2]], [[FERMT2]], HLA cluster (DRB5-DQA), [[INPP5D]], [[MEF2C]], MS4A cluster (MS4A3-[[MS4A6E]]), [[NME8]], [[PICALM]], [[PTK2B]], [[SLC24A4]], [[SORL1]], and [[ZCWPW1]] have been associated with Alzheimer's disease (AD) in large meta-analyses. We aimed to determine whether established AD-associated genes are associated with longitudinal cognitive decline by examining aggregate variation across these gene regions. In two single-sex cohorts of older, community-dwelling adults, we examined the association between SNPs in previously implicated gene regions and cognitive decline (age-adjusted person-specific cognitive slopes) using a Sequence Kernel Association Test (SKAT). In regions which showed aggregate significance, we examined the univariate association between individual SNPs in the region and cognitive decline. Only two of the original AD-associated SNPs were significantly associated with cognitive decline in our cohorts. We identified significant aggregate-level associations between cognitive decline and the gene regions [[BIN1]], [[CD33]], [[CELF1]], [[CR1]], HLA cluster, and [[MEF2C]] in the all-female cohort and significant associations with [[ABCA7]], HLA cluster, [[MS4A6E]], [[PICALM]], [[PTK2B]], [[SLC24A4]], and [[SORL1]] in the all-male cohort. We also identified a block of eight correlated SNPs in [[CD33]] and several blocks of correlated SNPs in [[CELF1]] that were significantly associated with cognitive decline in univariate analysis in the all-female cohort. 
|mesh-terms=* Aged
* Aging
* Alzheimer Disease
* Cognition Disorders
* DNA
* Female
* Genetic Association Studies
* Genetic Predisposition to Disease
* Humans
* Male
* Polymorphism, Single Nucleotide
|keywords=* Candidate AD genes
* Cognitive decline
* SNP associations
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5005889
}}
{{medline-entry
|title=Association of Alzheimer's disease GWAS loci with MRI markers of brain aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25670335
|abstract=Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N = 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p = 0.0054) and CD33 (rs3865444) with smaller intracranial volume (p = 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (p = 0.0006) and [[BIN1]] with HV (p = 0.00089). A weighted AD genetic risk score was associated with smaller HV (beta ± SE = -0.047 ± 0.013, p = 0.00041), even after excluding the APOE locus (p = 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons.
|mesh-terms=* Aging
* Alleles
* Alzheimer Disease
* Apolipoproteins E
* Brain
* Female
* Genome-Wide Association Study
* Hippocampus
* Humans
* Magnetic Resonance Imaging
* Male
* Organ Size
* Polymorphism, Single Nucleotide
* Risk
* Sialic Acid Binding Ig-like Lectin 3
|keywords=* Alzheimer
* GWAS
* Genetic risk score
* Hippocampal volume
* MRI-Markers
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391343
}}
{{medline-entry
|title=The benefits of staying active in old age: physical activity counteracts the negative influence of [[PICALM]], [[BIN1]], and [[CLU]] risk alleles on episodic memory functioning.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24660791
|abstract=[[PICALM]], [[BIN1]], [[CLU]], and [[APOE]] are top candidate genes for Alzheimer's disease, and they influence episodic memory performance in old age. Physical activity, however, has been shown to protect against age-related decline and counteract genetic influences on cognition. The aims of this study were to assess whether (a) a genetic risk constellation of [[PICALM]], [[BIN1]], and [[CLU]] polymorphisms influences cognitive performance in old age; and (b) if physical activity moderates this effect. Data from the SNAC-K population-based study were used, including 2,480 individuals (age range = 60 to 100 years) free of dementia at baseline and at 3- to 6-year follow-ups. Tasks assessing episodic memory, perceptual speed, knowledge, and verbal fluency were administered. Physical activity was measured using self-reports. Individuals who had engaged in frequent health- or fitness-enhancing activities within the past year were compared with those who were inactive. Genetic risk scores were computed based on an integration of risk alleles for [[PICALM]] (rs3851179 G allele, rs541458 T allele), [[BIN1]] (rs744373 G allele), and [[CLU]] (rs11136000 T allele). High genetic risk was associated with reduced episodic memory performance, controlling for age, education, vascular risk factors, chronic diseases, activities of daily living, and [[APOE]] gene status. Critically, physical activity attenuated the effects of genetic risk on episodic memory. Our findings suggest that participants with high genetic risk who maintain a physically active lifestyle show selective benefits in episodic memory performance.
|mesh-terms=* Adaptor Proteins, Signal Transducing
* Aged
* Aged, 80 and over
* Aging
* Alleles
* Alzheimer Disease
* Clusterin
* Cognition
* Exercise
* Female
* Genetic Predisposition to Disease
* Humans
* Male
* Memory, Episodic
* Middle Aged
* Monomeric Clathrin Assembly Proteins
* Nuclear Proteins
* Risk Factors
* Sweden
* Tumor Suppressor Proteins

|full-text-url=https://sci-hub.do/10.1037/a0035465
}}
{{medline-entry
|title=[[BIN1]] is decreased in sporadic but not familial Alzheimer's disease or in aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24205320
|abstract=Bridging integrator 1 ([[BIN1]]) has been implicated in sporadic Alzheimer's disease (AD) by a number of genome wide association studies (GWAS) in a variety of populations. Here we measured [[BIN1]] in frontal cortex samples from 24 sporadic AD and 24 age-matched non-dementia brains and correlated the expression of this protein with markers of AD. [[BIN1]] was reduced by 87% (p=0.007) in sporadic AD compared to non-dementia controls, but [[BIN1]] in sporadic AD did not correlate with soluble Aβ (r(s)=-0.084, p=0.698), insoluble Aβ (r(s)=0.237, p=0.269), Aβ plaque load (r(s)=0.063, p=0.771) or phospho-tau load (r(s)=-0.160, p=0.489). In contrast to our findings in sporadic AD, [[BIN1]] was unchanged in the hippocampus from 6 cases of familial AD compared to 6 age-matched controls (p=0.488). [[BIN1]] declined with age in a cohort of non-dementia control cases between 25 and 88 years but the correlation was not significant (rs=-0.449, p=0.081). Although [[BIN1]] is known to have a role in endocytosis, and the processing of the amyloid precursor protein ([[APP]]) to form amyloid-β (Aβ) peptides is dependent on endocytosis, knockdown of [[BIN1]] by targeted siRNA or the overexpression of [[BIN1]] in a human neuroblastoma cell line (SH-SY5Y) had no effect on [[APP]] processing. These data suggest that the alteration in [[BIN1]] is involved in the pathogenesis of sporadic, but not familial AD and is not a consequence of AD neurodegeneration or the ageing process, a finding in keeping with the numerous GWAS that implicate [[BIN1]] in sporadic AD. However, the mechanism of its contribution remains to be established.
|mesh-terms=* Adaptor Proteins, Signal Transducing
* Adult
* Aged
* Aged, 80 and over
* Aging
* Alzheimer Disease
* Cell Line, Tumor
* Female
* Gene Expression Regulation
* Gene Knockdown Techniques
* Humans
* Male
* Middle Aged
* Nuclear Proteins
* Tumor Suppressor Proteins

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804620
}}
{{medline-entry
|title=Genetic variants influencing human aging from late-onset Alzheimer's disease (LOAD) genome-wide association studies (GWAS).
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22445811
|abstract=Genetics plays a crucial role in human aging with up to 30% of those living to the mid-80s being determined by genetic variation. Survival to older ages likely entails an even greater genetic contribution. There is increasing evidence that genes implicated in age-related diseases, such as cancer and neuronal disease, play a role in affecting human life span. We have selected the 10 most promising late-onset Alzheimer's disease (LOAD) susceptibility genes identified through several recent large genome-wide association studies (GWAS). These 10 LOAD genes ([[APOE]], [[CLU]], [[PICALM]], [[CR1]], [[BIN1]], [[ABCA7]], [[MS4A6A]], [[CD33]], [[CD2AP]], and EPHA1) have been tested for association with human aging in our dataset (1385 samples with documented age at death [AAD], age range: 58-108 years; mean age at death: 80.2) using the most significant single nucleotide polymorphisms (SNPs) found in the previous studies. Apart from the [[APOE]] locus (rs2075650) which showed compelling evidence of association with risk on human life span (p = 5.27 × 10(-4)), none of the other LOAD gene loci demonstrated significant evidence of association. In addition to examining the known LOAD genes, we carried out analyses using age at death as a quantitative trait. No genome-wide significant SNPs were discovered. Increasing sample size and statistical power will be imperative to detect genuine aging-associated variants in the future. In this report, we also discuss issues relating to the analysis of genome-wide association studies data from different centers and the bioinformatic approach required to distinguish spurious genome-wide significant signals from real SNP associations.
|mesh-terms=* Age Distribution
* Aging
* Alzheimer Disease
* Chromosome Mapping
* Genetic Markers
* Genetic Predisposition to Disease
* Genetic Variation
* Genome-Wide Association Study
* Humans
* Polymorphism, Single Nucleotide
* Prevalence

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120742
}}