Role of Receptors in Relation to Plaques and Tangles in Alzheimer’s Disease Pathology

Abstract

Despite the identification of Aβ plaques and NFTs as biomarkers for Alzheimer’s disease (AD) pathology, therapeutic interventions remain elusive, with neither an absolute prophylactic nor a curative medication available to impede the progression of AD presently available. Current approaches focus on symptomatic treatments to maintain AD patients’ mental stability and behavioral symptoms by decreasing neuronal degeneration; however, the complexity of AD pathology requires a wide range of therapeutic approaches for both preventive and curative treatments. In this regard, this review summarizes the role of receptors as a potential target for treating AD and focuses on the path of major receptors which are responsible for AD progression. This review gives an overall idea centering on major receptors, their agonist and antagonist and future prospects of viral mimicry in AD pathology. This article aims to provide researchers and developers a comprehensive idea about the different receptors involved in AD pathogenesis that may lead to finding a new therapeutic strategy to treat AD.

Behavior of KCNQ Channels in Neural Plasticity and Motor Disorders

“…However, the future direction of KCNQ neural mechanosensation literature ought to focus more on the clinical and translational use of these pharmacotherapeutic options, as most of the literature used to support this review was based on animal models alone. Despite this, there is strong evidence that could support the initiation of future clinical trials, especially for auditory pathologies as well as in PD [ 14 , 80 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 ], and developments for understanding the effects that antimicrobial agents have on these potassium ion channels [ 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 ]. Additionally, the scope of this review was on neural modulation, yet there is a growing amount of literature on the behavior of KCNQ channels in cardiac modulations as well, especially in the cellular processes involved in arrhythmia [ 26 , 27 , 28 , 29 , 139 , 140 , 141 ,…”

“…This is where the literature ought to focus in order to determine if secondary factors that are not understood in these animal models also contribute to the memory impairment (i.e., hippocampal morphology) [ 90 , 91 , 92 , 93 , 94 , 95 ]. The epileptic phenotype, in conjunction with the cognitive impairment of these genetic models, may suggest additional psychomotor exploration [ 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 ].…”

“…While this avenue of study has proven to be a promising utilization of these K + channels in dopaminergic pathways, they are perhaps better associated with the treatment of motor disorders involving the neurotransmitter dopamine. Parkinson’s disease (PD) is a neurodegenerative disorder commonly associated with the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) [ 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 ]. As a result, the loss of nigrostriatal dopamine is associated with the motor symptoms classically observed in PD, such as muscular rigidity, bradykinesia, and tremor [ 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ].…”

“…However, it is important to note that retigabine was unable to completely prevent the occurrence of LID or delay the onset, even with chronic treatment. A limitation of retigabine as a pharmacotherapeutic option for the treatment of LID is its potential to induce sedation [ 102 , 103 , 104 , 105 ]. This effect, however, was reduced over the course of chronic treatment with retigabine.…”

Donepezil Beyond Alzheimer's Disease? A Narrative Review of Therapeutic Potentials of Donepezil in Different Diseases

“…Besides, one of the cell-destructive mechanisms in AD is glutamate toxic- ity and excitotoxicity process, which enhances the harmful effects of Aβ accumulation and tau pathology. Therefore, donepezil can play a protective role against these destructive processes by activating the Phosphatidylinositol 3-kinases/protein kinase B (PI3K-Akt) pathway and increasing α4 and α7 nicotinic receptors, which reduce the activation of N-methyl-D-aspartate (NMDA) receptors and apoptosis following calcium accumulation in the neurons (15,18,21,22). Donepezil also protects the hippocampus and cerebral cortex from oxidative stress by inhibiting glutathione reduction and reducing inflammatory processes (15,18,23,24).…”