Age‐related cognitive failure is a main devastating incident affecting even healthy people. Alzheimer's disease (AD) is the utmost common form of dementia among the geriatric community. In the pathogenesis of AD, cerebrovascular dysfunction is revealed before the beginning of the cognitive decline. Mounting proof shows a precarious impact of cerebrovascular dysregulation in the development of AD pathology. Recent studies document that the mammalian target of rapamycin (mTOR) acts as a crucial effector of cerebrovascular dysregulation in AD. The mTOR contributes to brain vascular dysfunction and subsequence cerebral blood flow deficits as well as cognitive impairment. Furthermore, mTOR causes the blood–brain barrier (BBB) breakdown in AD models. Inhibition of mTOR hyperactivity protects the BBB integrity in AD. Furthermore, mTOR drives cognitive defect and cerebrovascular dysfunction, which are greatly prevalent in AD, but the central molecular mechanisms underlying these alterations are obscure. This review represents the crucial and current research findings regarding the role of mTOR signaling in cognitive aging and cerebrovascular dysfunction in the pathogenesis of AD.
Neuropathic pain (NP) is the result of irregular processing in the central or peripheral nervous system, which is generally caused by neuronal injury. The management of NP represents a great challenge owing to its heterogeneous profile and the significant undesirable side effects of the frequently prescribed psychoactive agents, including benzodiazepines (BDZ). Currently, several established drugs including antidepressants, anticonvulsants, topical lidocaine, and opioids are used to treat NP, but they exert a wide range of adverse effects. To reduce the burden of adverse effects, we need to investigate alternative therapeutics for the management of NP. Flavonoids are the most common secondary metabolites of plants used in folkloric medicine as tranquilizers, and have been claimed to have a selective affinity to the BDZ binding site. Several studies in animal models have reported that flavonoids can reduce NP. In this paper, we emphasize the potentiality of flavonoids for the management of NP.
Objective:
Alzheimer's disease (AD) is a devastating neurodegenerative disorder, characterized
by the extracellular accumulations of amyloid beta (Aβ) as senile plaques and intracellular aggregations
of tau in the form of neurofibrillary tangles (NFTs) in specific brain regions. In this review, we
focus on the interaction of Aβ and tau with cytosolic proteins and several cell organelles as well as associated
neurotoxicity in AD.
Summary:
Misfolded proteins present in cells accompanied by correctly folded, intermediately folded,
as well as unfolded species. Misfolded proteins can be degraded or refolded properly with the aid of
chaperone proteins, which are playing a pivotal role in protein folding, trafficking as well as intermediate
stabilization in healthy cells. The continuous aggregation of misfolded proteins in the absence of
their proper clearance could result in amyloid disease including AD. The neuropathological changes of
AD brain include the atypical cellular accumulation of misfolded proteins as well as the loss of neurons
and synapses in the cerebral cortex and certain subcortical regions. The mechanism of neurodegeneration
in AD that leads to severe neuronal cell death and memory dysfunctions is not completely understood
until now.
Conclusion:
Examining the impact, as well as the consequences of protein misfolding, could help to
uncover the molecular etiologies behind the complicated AD pathogenesis.
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