HSOA journal of alzheimer's & neurodegenerative diseases最新文献

{"title":"Neurofilament Light (NF-L) Chain Protein from a Highly Polymerized Structural Component of the Neuronal Cytoskeleton to a Neurodegenerative Disease Biomarker in the Periphery.","authors":"Yuhai Zhao,&nbsp;Lisa Arceneaux,&nbsp;Frank Culicchia,&nbsp;Walter J Lukiw","doi":"10.24966/AND-9608/100056","DOIUrl":"10.24966/AND-9608/100056","url":null,"abstract":"<p><p>Neurofilaments (NFs) are critical scaffolding components of the axoskeleton of healthy neurons interacting directly with multiple synaptic-phosphoproteins to support and coordinate neuronal cell shape, cytoarchitecture, synaptogenesis and neurotransmission. While neuronal presynaptic proteins such as synapsin-2 (SYN II) degrade rapidly via the ubiquitin-proteasome pathway, a considerably more stable neurofilament light (NF-L) chain protein turns over much more slowly, and in several neurological diseases is accompanied by a pathological shift from an intracellular neuronal cytoplasmic location into various biofluid compartments. NF-L has been found to be significantly elevated in peripheral biofluids in multiple neurodegenerative disorders, however it is not as widely appreciated that NF-L expression within neurons undergoing inflammatory neurodegeneration exhibit a significant down-regulation in these neuron-specific intermediate-filament components. Down-regulated NF-L in neurons correlates well with the observed axonal and neuronal atrophy, neurite deterioration and synaptic disorganization in tissues affected by Alzheimer's disease (AD) and other progressive, age-related neurological diseases. This Review paper: <b>(i)</b> will briefly assess the remarkably high number of neurological disorders that exhibit NF-L depolymerization, liberation from neuron-specific compartments, mobilization and enrichment into pathological biofluids; <b>(ii)</b> will evaluate how NF-L exhibits compartmentalization effects in age-related neurological disorders; <b>(iii)</b> will review how the shift of NF-L compartmentalization from within the neuronal cytoskeleton into peripheral biofluids may be a diagnostic biomarker for neuronal-decline in all cause dementia most useful in distinguishing between closely related neurological disorders; and <b>(iv)</b> will review emerging evidence that deficits in plasma membrane barrier integrity, pathological transport and/or vesicle-mediated trafficking dysfunction of NF-L may contribute to neuronal decline, with specific reference to AD wherever possible.</p>","PeriodicalId":93439,"journal":{"name":"HSOA journal of alzheimer's & neurodegenerative diseases","volume":"7 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39704178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel API Coated Catheter Removes Amyloid-β from Plasma of Patients with Alzheimer's Disease.","authors":"Rishi Raj Chhipa,&nbsp;Omkar Gandbhir,&nbsp;Hao Le,&nbsp;Sadhana Sankar,&nbsp;Pazhani Sundaram","doi":"10.24966/and-9608/100055","DOIUrl":"https://doi.org/10.24966/and-9608/100055","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most common cause of dementia, characterized by the deposition of Amyloid-beta (Aβ) plaques in the brain. We have previously developed Amytrap peptide (the active pharmacological ingredient, API) and linked it to a sepharose bead matrix by click chemistry to form Amytrapper matrix, which was able to bind and remove Aβ from human sera and plasma spiked with biotinylated Aβ42 (bio-Aβ42) <i>in vitro</i>. To extend the logic of the previous studies, the current study investigates whether the Amytrap peptide coated inside a medically viable polycarbonate catheter (Amytrapper catheter) could bind and retain Aβ from the human sera. The Amytrapper matrix and the novel Amytrapper catheter were able to bind and retain spiked bio-Aβ42 from human sera or native Aβ from plasma of AD patients. Additional characteristics of the Amytrapper catheter are evaluated and presented in this study. The results presented here provide a proof-of-principle for the first time that extracorporeal Amytrapper device aids clearance of native Aβ (from plasma of AD patients). Thus, our device Amytrapper, either in the form of Sepharose matrix or catheter, could become a novel therapeutic strategy to remove Aβ from circulation in AD patients.</p>","PeriodicalId":93439,"journal":{"name":"HSOA journal of alzheimer's & neurodegenerative diseases","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39927566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}