An In-Silico Investigation of Key Lysine Residues and Their Selection for Clearing off A β and Holo-AβPP Through Ubiquitination

AbstractMalicious progression of neurodegeneration is a consequence of toxic aggregates of proteins or peptides such as amyloid beta (A β) reported in Alzheimer’s disease (AD). These aggregates hinder the electrochemical transmission at neuronal junctions and thus deteriorate neuronal-health by triggering dementia. Electrostatic and hydrophobic interactions among amino-acid residues are the governing principle behind the self-ass embly of aforesaid noxious oligomers or agglomerate. Interestingly, lysine residues are crucial for these interactions and for facilitating the clearance of toxic metabolites through the ubiquitination process. The mechanisms behind lysine selectivity and modifications of target proteins are very in triguing process and an avenue to explore the clearance of unwanted proteins from neurons. Therefore, it is fascinating for the researchers to investigate the role of key lysine, their selectivity and interactions with other amino acids to clear-off toxic products in exempting the progression of Neu rodegenerative disorders (NDDs). Herein, (1) we identified the aggregation prone sequence in Aβ40 and Aβ42 as ‘HHQKLVFFAE’ and ‘SGYEVHHQKLVFFAEDVG/KGAIIGLMVGGV’ respectively with critical lysine (K) at 16 and 28 for stabilizing the aggregates; (2) elucidated the interaction pattern of AβP P with other Alzheimer’s related proteins BACE1, APOE, SNCA, APBB1, CASP8, NAE1, ADAM10, and PSEN1 to describe the pat...
Source: Interdisciplinary Sciences, Computational Life Sciences - Category: Bioinformatics Source Type: research

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Publication date: Available online 15 February 2020Source: Neuroscience &Biobehavioral ReviewsAuthor(s): Filip Kosel, Jessica M.S. Pelley, Tamara B. FranklinAbstractTransgenic mouse models have been used extensively to model the cognitive impairments arising from Alzheimer’s disease (AD)-related pathology. However, less is known about the relationship between AD-related pathology and the behavioural and psychological symptoms of dementia (BPSD) commonly presented by patients. This review discusses the BPSD-like behaviours recapitulated by several mouse models of AD-related pathology, including the APP/PS1, Tg2576...
Source: Neuroscience and Biobehavioral Reviews - Category: Neuroscience Source Type: research
Photo credit Imon Godfrey Dear Carol:  My parents are in their 80s and have been fortunate with their health, but I worry about how they will do in the future. They still live in their home which we have made safer with some upgrades so that’s going fine for now. Any help they’ve needed has been provided by family members without too much disruption, so we consider ourselves fortunate. What worries me is that while I don’t see signs of actual dementia, at least from what I know about it, I do see them filling in for each other more often when it comes to words. Should we be worried about them and the...
Source: Minding Our Elders - Category: Geriatrics Authors: Source Type: blogs
Authors: Rao GP, Sivakumar PT, Srivastava S, Sidana RC PMID: 32055061 [PubMed]
Source: Indian Journal of Psychiatry - Category: Psychiatry Tags: Indian J Psychiatry Source Type: research
Authors: Niznik JD, Zhao X, He M, Aspinall SL, Hanlon JT, Nace D, Thorpe JM, Thorpe CT Abstract INTRODUCTION: We evaluated the impact of deprescribing acetylcholinesterase inhibitors (AChEIs) on aggressive behaviors and incident antipsychotic use in nursing home (NH) residents with severe dementia. METHODS: We conducted a retrospective study of Medicare claims, Part D, Minimum Data Set for NH residents aged 65+ with severe dementia receiving AChEIs in 2016. Aggressive behaviors were measured using the aggressive behavior scale (ABS; n = 30,788). Incident antipsychotic prescriptions were evaluated among antipsyc...
Source: The Journal of Alzheimers Association - Category: Psychiatry Tags: Alzheimers Dement Source Type: research
BACKGROUND: Learning to walk with a 4-wheeled walker increases cognitive demands in people with Alzheimer's dementia (AD). However, it is expected that experience will offset the increased cognitive demand. Current research has not yet evaluated gait in pe...
Source: SafetyLit - Category: International Medicine & Public Health Tags: Age: Elder Adults Source Type: news
Traumatic brain injury (TBI) can cause persistent cognitive changes and ongoing neurodegeneration in the brain. Accumulating epidemiological and pathological evidence implicates TBI in the development of Alzheimer's disease (AD), the most common cause of d...
Source: SafetyLit - Category: International Medicine & Public Health Tags: Age: Elder Adults Source Type: news
Contributors : Xiaolai Zhou ; Alexandra M Nicholson ; Yingxue Ren ; Mieu Brooks ; Peizhou Jiang ; Aamir Zuberi ; Hung N Phuoc ; Ralph B Perkerson ; Billie Matchett ; Tammee M Parsons ; NiCole A Finch ; Wenlang Lin ; Wenhui Qiao ; Monica Castanedes-Casey ; Virginia Phillips ; Ariston L Librero ; Yan Asmann ; Guojun Bu ; Melissa E Murray ; Cathleen Lutz ; Dennis W Dickson ; Rosa RademakersSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusGenetic variants that define two distinct haplotypes at the TMEM106B locus have been implicated in multiple neurodegenerative diseases and in healthy bra...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
DR MAX PEMBERTON: Being optimistic isn't about being in denial, it's about trying to find the positives in life, even in dire situations.
Source: the Mail online | Health - Category: Consumer Health News Source Type: news
I once saw an older gentleman who was mentally impaired from birth. A hard enough blow, he had slowly, inexorably drifted into dementia.   He cut his head in a fall, suffering the ravages of gravity as so many do every day, every night. He was Caucasian.  His full-time care-giver was African-American.  That young man was […]Find jobs at  Careers by KevinMD.com.  Search thousands of physician, PA, NP, and CRNA jobs now.  Learn more.
Source: Kevin, M.D. - Medical Weblog - Category: General Medicine Authors: Tags: Physician Emergency Medicine Source Type: blogs
Publication date: Available online 13 February 2020Source: NeuronAuthor(s): Juan A. Ortega, Elizabeth L. Daley, Sukhleen Kour, Marisa Samani, Liana Tellez, Haley S. Smith, Elizabeth A. Hall, Y. Taylan Esengul, Yung-Hsu Tsai, Tania F. Gendron, Christopher J. Donnelly, Teepu Siddique, Jeffrey N. Savas, Udai B. Pandey, Evangelos KiskinisSummaryThe most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is a hexanucleotide repeat expansion in C9orf72 (C9-HRE). While RNA and dipeptide repeats produced by C9-HRE disrupt nucleocytoplasmic transport, the proteins that become redistributed...
Source: Neuron - Category: Neuroscience Source Type: research
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