scholarly journals Alterations of Ca2+-responsive proteins within cholinergic neurons in aging and Alzheimer's disease

2014 ◽  
Vol 35 (6) ◽  
pp. 1325-1333 ◽  
Author(s):  
David Riascos ◽  
Alexander Nicholas ◽  
Ravand Samaeekia ◽  
Rustam Yukhananov ◽  
M.-Marsel Mesulam ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinergic Neurons

In silico screening of pyridoxine carbamates for Anti-Alzheimer’s activities

2020 ◽  
Vol 20 ◽  
Author(s):  
Dnyaneshwar Baswar ◽  
Abha Sharma ◽  
Awanish Mishra
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
In Silico ◽  
Neurodegenerative Disorder ◽  
Biological Activities ◽  
Cholinergic Neurons ◽  
In Silico Screening ◽  
In Silico Studies ◽  
Bbb Permeability ◽  
Ld50 Value

Background: Alzheimer’s disease (AD), an irreversible complex neurodegenerative disorder, is most common type of dementia, with progressive loss of cholinergic neurons. Based on the multi- factorial etiology of Alzheimer’s disease, novel ligands strategy appears as up-coming approach for the development of newer molecules against AD. This study is envisaged to investigate anti-Alzheimer’s potential of 10 synthesized compounds. The screening of compounds (1-10) was carried out using in silico techniques. Methods: For in silico screening of physicochemical properties of compounds molinspiration property engine v.2018.03, Swiss ADME online web-server and pkCSM ADME were used. For pharmacodynamic prediction PASS software while toxicity profile of compounds were analyzed through ProTox-II online software. Simultaneously, molecular docking analysis was performed on mouse AChE enzyme (PDB ID:2JGE, obtained from RSCB PDB) using Auto Dock Tools 1.5.6. Results: Based on in silico studies, compound 9 and 10 have been found to have better drug likeness, LD50 value, and better anti-Alzheimer’s, nootropic activities. However, these compounds had poor blood brain barrier (BBB) permeability. Compound 4 and 9 were predicted with better docking score for AChE enzyme. Conclusion: The outcome of in silico studies have suggested, out of various substitutions at different positions of pyridoxine-carbamate, compound 9 have shown promising drug likeness, with better safety and efficacy profile for anti-Alzheimer’s activity. However, BBB permeability appears as one the major limitation of all these compounds. Further studies are required to confirm its biological activities.

Current Strategies and Novel Drug Approaches for Alzheimer Disease

2020 ◽  
Vol 19 (9) ◽  
pp. 676-690 ◽  
Author(s):  
Roma Ghai ◽  
Kandasamy Nagarajan ◽  
Meenakshi Arora ◽  
Parul Grover ◽  
Nazakat Ali ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinergic Neurons ◽  
Amyloid Plaque ◽  
Neural Pathways ◽  
Current Trends ◽  
Personality Changes ◽  
Traditional Therapies ◽  
Novel Drug ◽  
The Brain

Alzheimer’s Disease (AD) is a chronic, devastating dysfunction of neurons in the brain leading to dementia. It mainly arises due to neuronal injury in the cerebral cortex and hippocampus area of the brain and is clinically manifested as a progressive mental failure, disordered cognitive functions, personality changes, reduced verbal fluency and impairment of speech. The pathology behind AD is the formation of intraneuronal fibrillary tangles, deposition of amyloid plaque and decline in choline acetyltransferase and loss of cholinergic neurons. Tragically, the disease cannot be cured, but its progression can be halted. Various cholinesterase inhibitors available in the market like Tacrine, Donepezil, Galantamine, Rivastigmine, etc. are being used to manage the symptoms of Alzheimer’s disease. The paper’s objective is to throw light not only on the cellular/genetic basis of the disease, but also on the current trends and various strategies of treatment including the use of phytopharmaceuticals and nutraceuticals. Enormous literature survey was conducted and published articles of PubMed, Scifinder, Google Scholar, Clinical Trials.org and Alzheimer Association reports were studied intensively to consolidate the information on the strategies available to combat Alzheimer’s disease. Currently, several strategies are being investigated for the treatment of Alzheimer’s disease. Immunotherapies targeting amyloid-beta plaques, tau protein and neural pathways are undergoing clinical trials. Moreover, antisense oligonucleotide methodologies are being approached as therapies for its management. Phytopharmaceuticals and nutraceuticals are also gaining attention in overcoming the symptoms related to AD. The present review article concludes that novel and traditional therapies simultaneously promise future hope for AD treatment.

scholarly journals Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Jose L. Martinez ◽  
Matthew D. Zammit ◽  
Nicole R. West ◽  
Bradley T. Christian ◽  
Anita Bhattacharyya
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Basal Forebrain ◽  
Critical Role ◽  
Memory Loss ◽  
Cholinergic Neurons ◽  
Cholinergic Innervation ◽  
Attention And Memory ◽  
Basal Forebrain Cholinergic Neurons

Down syndrome (DS, trisomy 21) is characterized by intellectual impairment at birth and Alzheimer’s disease (AD) pathology in middle age. As individuals with DS age, their cognitive functions decline as they develop AD pathology. The susceptibility to degeneration of a subset of neurons, known as basal forebrain cholinergic neurons (BFCNs), in DS and AD is a critical link between cognitive impairment and neurodegeneration in both disorders. BFCNs are the primary source of cholinergic innervation to the cerebral cortex and hippocampus, as well as the amygdala. They play a critical role in the processing of information related to cognitive function and are directly engaged in regulating circuits of attention and memory throughout the lifespan. Given the importance of BFCNs in attention and memory, it is not surprising that these neurons contribute to dysfunctional neuronal circuitry in DS and are vulnerable in adults with DS and AD, where their degeneration leads to memory loss and disturbance in language. BFCNs are thus a relevant cell target for therapeutics for both DS and AD but, despite some success, efforts in this area have waned. There are gaps in our knowledge of BFCN vulnerability that preclude our ability to effectively design interventions. Here, we review the role of BFCN function and degeneration in AD and DS and identify under-studied aspects of BFCN biology. The current gaps in BFCN relevant imaging studies, therapeutics, and human models limit our insight into the mechanistic vulnerability of BFCNs in individuals with DS and AD.

Evidence for the presence of antibodies to cholinergic neurons in the serum of patients with Alzheimer's disease

1988 ◽  
Vol 235 (8) ◽  
pp. 466-471 ◽  
Author(s):  
P. Foley ◽  
H. F. Bradford ◽  
M. Docherty ◽  
H. Fillit ◽  
V. N. Luine ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinergic Neurons

Profiling Basal Forebrain Cholinergic Neurons Reveals a Molecular Basis for Vulnerability Within the Ts65Dn Model of Down Syndrome and Alzheimer’s Disease

2020 ◽  
Author(s):  
Melissa J. Alldred ◽  
Sai C. Penikalapati ◽  
Sang Han Lee ◽  
Adriana Heguy ◽  
Panos Roussos ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Basal Forebrain ◽  
Differentially Expressed Gene ◽  
Cholinergic Neurons ◽  
Bioinformatic Analysis ◽  
Selective Vulnerability ◽  
Neuronal Population ◽  
Single Population

Abstract Background: Basal forebrain cholinergic neuron (BFCN) degeneration is a hallmark of Down syndrome (DS) and Alzheimer’s disease (AD). Current therapeutics have been unsuccessful in slowing disease progression, likely due to complex pathological interactions and dysregulated pathways that are poorly understood. The Ts65Dn trisomic mouse model recapitulates both cognitive and morphological deficits of DS and AD, including BFCN degeneration. Methods: We utilized Ts65Dn mice to understand mechanisms underlying BFCN degeneration to identify novel targets for therapeutic intervention. We performed high-throughput, single population RNA sequencing (RNA-seq) to interrogate transcriptomic changes within medial septal nucleus (MSN) BFCNs, using laser capture microdissection to individually isolate ~500 choline acetyltransferase-immunopositive neurons in Ts65Dn and normal disomic (2N) mice at 6 months of age (MO). Results: Ts65Dn mice had unique MSN BFCNs transcriptomic profiles at ~6 MO clearly differentiating them from 2N mice. Leveraging Ingenuity Pathway Analysis and KEGG analysis, we linked differentially expressed gene (DEG) changes within MSN BFCNs to several canonical pathways and aberrant physiological functions. The dysregulated transcriptomic profile of trisomic BFCNs provides key information underscoring selective vulnerability within the septohippocampal circuit. Conclusions: We propose both expected and novel therapeutic targets for DS and AD, including specific DEGs within cholinergic, glutamate, GABAergic, and neurotrophin pathways, as well as select targets for repairing oxidative phosphorylation status in neurons. We demonstrate and validate an interrogative quantitative bioinformatic analysis of a key dysregulated neuronal population linking single population transcript changes to an established pathological hallmark associated with cognitive decline for therapeutic development in human DS and AD.

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