Next Generation Precision Medicine: CRISPR-mediated Genome Editing for the Treatment of Neurodegenerative Disorders

AbstractDespite significant advancements in the field of molecular neurobiology especially neuroinflammation and neurodegeneration, the highly complex molecular mechanisms underlying neurodegenerative diseases remain elusive. As a result, the development of the next generation neurotherapeutics has experienced a considerable lag phase. Recent advancements in the field of genome editing offer a new template for dissecting the precise molecular pathways underlying the complex neurodegenerative disorders. We believe that the innovative genome and transcriptome editing strategies offer an excellent opportunity to decipher novel therapeutic targets, develop novel neurodegenerative disease models, develop neuroimaging modalities, develop next-generation diagnostics as well as develop patient-specific precision-targeted personalized therapies to effectively treat neurodegenerative disorders including Alzheimer ’s disease, Parkinson’s disease, Huntington’s disease, Amyotrophic lateral sclerosis, Frontotemporal dementia etc. Here, we review the latest developments in the field of CRISPR-mediated genome editing and provide unbiased futuristic insights regarding its translational potential to improve th e treatment outcomes and minimize financial burden. However, despite significant advancements, we would caution the scientific community that since the CRISPR field is still evolving, currently we do not know the full spectrum of CRISPR-mediated side effects. In the wak...
Source: Journal of NeuroImmune Pharmacology - Category: Drugs & Pharmacology Source Type: research

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This study provides strong evidence that following a healthy lifestyle can substantially extend the years a person lives disease-free." Commentary on Recent Evidence for Cognitive Decline to Precede Amyloid Aggregation in Alzheimer's Disease https://www.fightaging.org/archives/2020/01/commentary-on-recent-evidence-for-cognitive-decline-to-precede-amyloid-aggregation-in-alzheimers-disease/ I can't say that I think the data presented in the research noted here merits quite the degree of the attention that it has been given in the popular science press. It is interesting, but not compelling if its role...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract The global burden of neurodegenerative diseases is alarmingly increasing in parallel to the aging of population. Although the molecular mechanisms leading to neurodegeneration are not completely understood, excitotoxicity, defined as to the injury and death of neurons due to an excessive or prolonged exposure to excitatory amino acids, has been shown to play a pivotal role. The increased release and/or decreased uptake of glutamate results in a dysregulation of neuronal calcium homeostasis, leading to oxidative stress, mitochondrial dysfunctions, disturbances in protein turn-over and neuroinflammation. De...
Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research
Xiao Neurodegenerative diseases (NDs) affect millions of people worldwide. Characterized by the functional loss and death of neurons, NDs lead to symptoms (dementia and seizures) that affect the daily lives of patients. In spite of extensive research into NDs, the number of approved drugs for their treatment remains limited. There is therefore an urgent need to develop new approaches for the prevention and treatment of NDs. Glycans (carbohydrate chains) are ubiquitous, abundant, and structural complex natural biopolymers. Glycans often covalently attach to proteins and lipids to regulate cellular recognition, adhes...
Source: Molecules - Category: Chemistry Authors: Tags: Review Source Type: research
AbstractOver the last two decades, a number of studies have underlined the importance of lysosomal ‐based degradative pathways in maintaining the homeostasis of post‐mitotic cells, and revealed the remarkable contribution of a functional autophagic machinery in the promotion of longevity. In contrast, defects in the clearance of organelles and aberrant protein aggregates have been linked to a ccelerated neuronal loss and neurological dysfunction. Several neurodegenerative disorders, among which Alzheimer disease (AD), Frontotemporal dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) to name a few, are associated wi...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: Review Source Type: research
Conclusions: Our results support the consensus that the R47H variant is significantly associated with AD. However, we did not find evidence for association of the R47H variant with other neurodegenerative diseases.
Source: Alzheimer Disease and Associated Disorders - Category: Geriatrics Tags: Original Articles Source Type: research
CONCLUSIONS: Our results support the consensus that the R47H variant is significantly associated with AD. However, we did not find evidence for association of the R47H variant with other neurodegenerative diseases. PMID: 31513029 [PubMed - as supplied by publisher]
Source: Alzheimer Disease and Associated Disorders - Category: Psychiatry Tags: Alzheimer Dis Assoc Disord Source Type: research
Publication date: Available online 21 August 2019Source: Molecular and Cellular NeuroscienceAuthor(s): Ju Gao, Luwen Wang, Tingxiang Yan, George Perry, Xinglong WangAbstractGenetic mutations in TAR DNA-binding protein 43 (TDP-43) cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Importantly, TDP-43 proteinopathy, characterized by aberrant phosphorylation, ubiquitination, cleavage or nuclear depletion of TDP-43 in neurons and glial cells, is a common prominent pathological feature of various major neurodegenerative diseases including ALS, FTD, and Alzheimer's disease (AD). Although the pathomechan...
Source: Molecular and Cellular Neuroscience - Category: Neuroscience Source Type: research
Seventy years of research on Western Pacific amyotrophic lateral sclerosis and parkinsonism-dementia (ALS/PDC) has provided invaluable data on the etiology, molecular pathogenesis and latency of this disappearing environmental neurodegenerative disease. ALS/PDC is linked to genotoxic chemicals (notably methylazoxymethanol, MAM) derived from seed of the cycad plant (Cycas spp) which was used as a traditional food and/or medicine in all three affected Western Pacific populations. MAM, nitrosamines and hydrazines generate methyl free radicals which damage DNA (O6-methylguanine) that can induce mutations in cycling cells and d...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
CONCLUSIONS: The varied pharmacologic mechanisms of NBP involve many complex molecular mechanisms; however, there many unknown pharmacologic effects await further study. PMID: 31205106 [PubMed - in process]
Source: Chinese Medical Journal - Category: General Medicine Authors: Tags: Chin Med J (Engl) Source Type: research
AbstractLysosomes are acidic, membrane-bound organelles that serve as the primary catabolic compartment of the cell. They are crucial to a variety of cellular processes from nutrient storage to autophagy. Given the diversity of lysosomal functions, it is unsurprising that lysosomes are also emerging as important players in aging. Lysosomal dysfunction is implicated in several aging-related neurodegenerative diseases including Alzheimer ’s, Parkinson’s, amyotrophic lateral sclerosis/frontotemporal dementia, and Huntington’s. Although the precise role of lysosomes in the aging brain is not well-elucidated, ...
Source: Neurotherapeutics - Category: Neurology Source Type: research
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