Unstable mutations and neurodegenerative disorders

1998 ◽  
Vol 245 (8) ◽  
pp. 505-510 ◽  
Author(s):  
A. Brice
Keyword(s):  
Neurodegenerative Disorders ◽  
Unstable Mutations

Insights into amyloid disease from fly models

2014 ◽  
Vol 56 ◽  
pp. 69-83 ◽  
Author(s):  
Ko-Fan Chen ◽  
Damian C. Crowther
Keyword(s):  
Drosophila Melanogaster ◽  
Neurodegenerative Disorders ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Disease Pathogenesis ◽  
Amyloid Aggregates ◽  
Aβ Amyloid ◽  
Polypeptide Chains ◽  
Amyloid Diseases

The formation of amyloid aggregates is a feature of most, if not all, polypeptide chains. In vivo modelling of this process has been undertaken in the fruitfly Drosophila melanogaster with remarkable success. Models of both neurological and systemic amyloid diseases have been generated and have informed our understanding of disease pathogenesis in two main ways. First, the toxic amyloid species have been at least partially characterized, for example in the case of the Aβ (amyloid β-peptide) associated with Alzheimer's disease. Secondly, the genetic underpinning of model disease-linked phenotypes has been characterized for a number of neurodegenerative disorders. The current challenge is to integrate our understanding of disease-linked processes in the fly with our growing knowledge of human disease, for the benefit of patients.

Polyphenol health effects on cardiovascular and neurodegenerative disorders: a meta-analysis

2019 ◽  
Author(s):  
Giorgia Spaggiari ◽  
Francesco Poti ◽  
Francesca Zimetti ◽  
Ilaria Zanotti ◽  
Daniele Santi
Keyword(s):  
Health Effects ◽  
Neurodegenerative Disorders ◽  
Meta Analysis

Preliminary outcomes in transcutaneous neuromuscular electrical stimulation use in patients with dysphagia

2018 ◽  
Vol 8 (31) ◽  
pp. 167-174
Author(s):  
Codrut Sarafoleanu ◽  
Raluca Enache
Keyword(s):  
Traumatic Brain Injury ◽  
Head And Neck Cancer ◽  
Electrical Stimulation ◽  
Neurodegenerative Disorders ◽  
Structural Changes ◽  
Congenital Abnormalities ◽  
Neuromuscular Electrical Stimulation ◽  
Therapy Options ◽  
Dysphagia Treatment ◽  
Risk Of Aspiration

Abstract Dysphagia is a common disorder associated with a large number of etiologies like aging, stroke, traumatic brain injury, head and neck cancer, neurodegenerative disorders, structural changes or congenital abnormalities. The type of the treatment and its results depend on the type, severity and the cause of dysphagia. The primary goal of dysphagia treatment is to improve the swallowing process and decrease the risk of aspiration. Along with the existing rehabilitation swallowing treatments, new adjunctive therapy options developed, one of them being the neuromuscular electrical stimulation (NMES). The authors present the principles of NMES, a small literature review about the results of this therapy and their experience in using transcutaneous NMES in dysphagia patients.

An Anthrone-Based Kv7.2/7.3 Channel Blocker with Improved Properties for the Investigation of Psychiatric and Neurodegenerative Disorders

2019 ◽  
Author(s):  
Jacob Porter ◽  
Oscar Vivas-Rodriguez ◽  
C. David Weaver ◽  
Eamonn Dickson ◽  
Abdulmohsen Alsafran ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Neurodegenerative Disorders ◽  
Channel Blocker ◽  
Optimal Combination ◽  
Channel Blockers ◽  
Enolate Alkylation ◽  
Cyp Inhibition ◽  
Alkylation Reactions ◽  
Metabolic Instability

A set of novel Kv7.2/7.3 (KCNQ2/3) channel blockers was synthesized to address several liabilities of the known compounds XE991 (metabolic instability and CYP inhibition) and the clinical compound DMP 543 (acid instability, insolubility, and lipophilicity). Using the anthrone scaffold of the prior channel blockers, alternative heteroarylmethyl substituents were installed via enolate alkylation reactions. Incorporation of a pyridazine and a fluorinated pyridine gave an analog (JDP-107) with an optimal combination of potency (IC<sub>50</sub>= 0.16 𝜇M in a Kv7.2 thallium flux assay), efficacy in a Kv7.2/7.3 patch clamp assay, and drug-like properties.

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