Significance of Choline Acetyltransferase Enzyme in Tackling Neurodegenerative Diseases

Bagwe, Pritam V.; Sathaye, Sadhana

doi:10.1007/s40610-022-00148-9

Curr Mol Bio Rep

2022

DOI: 10.1007/s40610-022-00148-9

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Significance of Choline Acetyltransferase Enzyme in Tackling Neurodegenerative Diseases

Pritam V. Bagwe

Sadhana Sathaye

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2024

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Cited by 3 publications

References 89 publications

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Synthesis, characterization, DFT, AMDET and molecular docking reveals the binding mechanism of hydroxyl containing bis-Schiff base derivatives: An approach toward Alzheimer disease

Arif,

Khan,

Iqbal

et al. 2024

Results in Chemistry

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Synthesis, characterization, DFT, AMDET and molecular docking reveals the binding mechanism of hydroxyl containing bis-Schiff base derivatives: An approach toward Alzheimer disease

Arif,

Khan,

Iqbal

et al. 2024

Results in Chemistry

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Neural landscape is associated with functional outcomes in irradiated patients with oropharyngeal squamous cell carcinoma

Islam,

Gleber-Netto,

Mulcahy

et al. 2024

Sci. Transl. Med.

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The incidence of human papilloma virus–mediated oropharyngeal squamous cell carcinoma (OPSCC) has increased over the past 40 years, particularly among young individuals with a favorable prognosis; however, current therapy often leads to unfortunate side effects, such as dysphagia. Despite the emphasis on dysphagia in previous studies, there is an important research gap in understanding the correlation between neuronal changes and patient-reported and functional outcomes in patients with OPSCC. To address this issue, we examined pathologic tissue samples from patients with OPSCC using multiplex immunofluorescence staining and machine learning to correlate tumor-associated neuronal changes with prospectively collected patient-reported and functional outcomes. We found that tumor enrichment of adrenergic (TH + ) and CGRP + sensory–afferent nerves correlated with poorer swallowing outcomes. Functional electromyography recordings showed correlations between growing (GAP43 + ) and immature cholinergic (ChAT + DCX + ) nerves and denervation patterns in survivors of OPSCC. A murine model of radiation-induced dysphagia further confirmed that immature cholinergic and CGRP + nerves were correlated with impaired swallowing. Preclinical interventional studies also supported the independent contributions of CGRP + and cholinergic (ChAT + ) nerves to dysphagia in treated mouse models of OPSCC. Our results suggest that CGRP + and ChAT + neuronal signaling play distinct roles in tumor- and radiation-induced dysphagia in OPSCC and offer a comprehensive dataset on the neural landscape of OPSCC. These insights may guide early interventions for swallow preservation and the repurposing of neurology-related drugs, such as CGRP blockers, in clinical oncology and survivorship.

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Hypoxic preconditioning in rats with low and high prepulse inhibition of acoustic startle is implemented through topographically different sensory inputs. Working hypothesis

Zakharova,

Storozheva,

Proshin

et al. 2024

Zhurnal Vysshei Nervnoi Deyatelnosti Imeni I.P. Pavlova

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The neurotransmitter and network mechanisms of hypoxic preconditioning are practically unknown. Previously, in rats, we identified the key role of the hippocampus and its cholinergic projections in the preconditioning mechanism of single-exposure of moderate hypobaric hypoxia (HBH) based on the association between the efficiency of HBH and the magnitude of Prepulse Inhibition of Acoustic Startle (PPI). This study presents the first data on PPI-dependent neuronal networks of hypoxic preconditioning and their cholinergic components. The activity of synaptic choline acetyltransferase (ChAT), an indicator of cholinergic function, was used for a correlation analysis of ChAT response to HBH in the hippocampus, cerebral cortex, and caudal brainstem in animals with different levels of PPI. In rats with PPI 40%, ChAT activity was correlated in the hippocampus, cortex and caudal brainstem, while in rats with PPI 40% in the hippocampus and cortex. It is hypothesized that HBH is realized through topographically different sensory inputs, namely through respiratory neurons of the brainstem in rats with low PPI and respiratory neurons of the olfactory epithelium in rats with high PPI.

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Significance of Choline Acetyltransferase Enzyme in Tackling Neurodegenerative Diseases

Cited by 3 publications

References 89 publications

Synthesis, characterization, DFT, AMDET and molecular docking reveals the binding mechanism of hydroxyl containing bis-Schiff base derivatives: An approach toward Alzheimer disease

Synthesis, characterization, DFT, AMDET and molecular docking reveals the binding mechanism of hydroxyl containing bis-Schiff base derivatives: An approach toward Alzheimer disease

Neural landscape is associated with functional outcomes in irradiated patients with oropharyngeal squamous cell carcinoma

Hypoxic preconditioning in rats with low and high prepulse inhibition of acoustic startle is implemented through topographically different sensory inputs. Working hypothesis

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