Exploring ER stress response in cellular aging and neuroinflammation in Alzheimer's disease

Uddin, Md. Sahab; Yu, Wing Shan; Lim, Lee Wei

doi:10.1016/j.arr.2021.101417

Cited by 61 publications

(34 citation statements)

References 251 publications

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“…The relationship between ER stress and inflammation in the CNS is well-known [ 21 ]. Neuroinflammation involves astrocytes, the main cell type expressing Dio2 in the CNS, hence the probable site where ER stress is triggered.…”

Section: Discussionmentioning

confidence: 99%

“…The characteristic signatures of “brain aging” include, among other elements, a cumulative buildup of neuroinflammation [ 25 ], particularly in the hippocampus, cerebral cortex, and cerebellum [ 26 , 27 , 28 ]. The cumulative buildup of dysfunctional proteins and an unfolded protein response, markers of ER stress also correlate with changes in cognition [ 21 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

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Age Worsens the Cognitive Phenotype in Mice Carrying the Thr92Ala-DIO2 Polymorphism

et al. 2022

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The Thr92Ala-Dio2 polymorphism has been associated with reduced cognition in 2-month-old male mice and increased risk for cognitive impairment and Alzheimer’s disease in African Americans. This has been attributed to reduced thyroid hormone (TH) signaling and endoplasmic reticulum (ER) stress in the brain. Here we studied the Thr92Ala-Dio2 mouse model and saw that older male mice (7–8-month-old) exhibited a more severe cognition impairment, which extended to different aspects of declarative and working memories. A similar phenotype was observed in 4–5-month-old female mice. There were no structural alterations in the prefrontal cortex (PFC) and hippocampus of the Thr92Ala-Dio2 mouse. Nonetheless, in both male and female PFC, there was an enrichment in genes associated with TH-dependent processes, ER stress, and Golgi apparatus, while in the hippocampus there was additional enrichment in genes associated with inflammation and apoptosis. Reduced TH signaling remains a key mechanism of disease given that short-term treatment with L-T3 rescued the cognitive phenotype observed in males and females. We conclude that in mice, age is an additional risk factor for cognitive impairment associated with the Thr92Ala-Dio2 polymorphism. In addition to reduced TH signaling, ER-stress, and involvement of the Golgi apparatus, hippocampal inflammation and apoptosis were identified as potentially important mechanisms of a disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Age Worsens the Cognitive Phenotype in Mice Carrying the Thr92Ala-DIO2 Polymorphism

et al. 2022

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“…Hence, the use of mushrooms with beneficial health effects in humans requires in vivo experimentation to ensure their safety and efficacy. Aqueous extracts of HE rich in polysaccharides were shown to promote neuronal growth and differentiation [ 17 , 23 , 51 , 52 , 53 ] via the reduction in endoplasmic reticulum stress-induced cell atrophy, expression of neurotrophic factors in astrocytes, and decrease in neurodegenerative-induced cell atrophy [ 51 , 54 , 55 , 56 ]. The mechanism of action of HE has been further investigated in several preclinical studies.…”

Section: Preclinical Studies Of Hericium Erinaceus ...mentioning

confidence: 99%

The Monkey Head Mushroom and Memory Enhancement in Alzheimer’s Disease

Yanshree

Fung

et al. 2022

Cells

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Alzheimer’s disease (AD) is a neurodegenerative disorder, and no effective treatments are available to treat this disorder. Therefore, researchers have been investigating Hericium erinaceus, or the monkey head mushroom, an edible medicinal mushroom, as a possible treatment for AD. In this narrative review, we evaluated six preclinical and three clinical studies of the therapeutic effects of Hericium erinaceus on AD. Preclinical trials have successfully demonstrated that extracts and bioactive compounds of Hericium erinaceus have potential beneficial effects in ameliorating cognitive functioning and behavioral deficits in animal models of AD. A limited number of clinical studies have been conducted and several clinical trials are ongoing, which have thus far shown analogous outcomes to the preclinical studies. Nonetheless, future research on Hericium erinaceus needs to focus on elucidating the specific neuroprotective mechanisms and the target sites in AD. Additionally, standardized treatment parameters and universal regulatory systems need to be established to further ensure treatment safety and efficacy. In conclusion, Hericium erinaceus has therapeutic potential and may facilitate memory enhancement in patients with AD.

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“…A key driver of these changes is thought to be aging-associated neuroinflammation, which also appears to differentially impact specific vulnerable cell populations in the brain ( Sparkman and Johnson, 2008 ; Simen et al, 2011 ; Mattson and Arumugam, 2018 ). Correlated with these changes is the compromised structural/functional integrity of mitochondria and impaired neuronal bioenergetics, cumulative buildup of dysfunctional proteins and an unfolded protein response, markers of endoplasmic reticulum (ER) stress, failure to effectively scavenge reactive oxygen species (ROS) and oxidative damage, overlaid on a baseline substratum of neuroinflammatory changes, namely a disrupted cytokine milieu and microglial activation ( Wyss-Coray, 2016 ; Mattson and Arumugam, 2018 ; Webb and Sideris, 2020 ; Uddin et al, 2021 ). While these changes overlap and correlate with each other, the causal association between these events still remains unclear.…”

Section: Hallmark Signatures Of Brain Agingmentioning

confidence: 99%

Early Adversity and Accelerated Brain Aging: A Mini-Review

Chaudhari

Singla

Vaidya

2022

Front. Mol. Neurosci.

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Early adversity is an important risk factor that influences brain aging. Diverse animal models of early adversity, including gestational stress and postnatal paradigms disrupting dam-pup interactions evoke not only persistent neuroendocrine dysfunction and anxio-depressive behaviors, but also perturb the trajectory of healthy brain aging. The process of brain aging is thought to involve hallmark features such as mitochondrial dysfunction and oxidative stress, evoking impairments in neuronal bioenergetics. Furthermore, brain aging is associated with disrupted proteostasis, progressively defective epigenetic and DNA repair mechanisms, the build-up of neuroinflammatory states, thus cumulatively driving cellular senescence, neuronal and cognitive decline. Early adversity is hypothesized to evoke an “allostatic load” via an influence on several of the key physiological processes that define the trajectory of healthy brain aging. In this review we discuss the evidence that animal models of early adversity impinge on fundamental mechanisms of brain aging, setting up a substratum that can accelerate and compromise the time-line and nature of brain aging, and increase risk for aging-associated neuropathologies.

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Exploring ER stress response in cellular aging and neuroinflammation in Alzheimer's disease

Cited by 61 publications

References 251 publications

Age Worsens the Cognitive Phenotype in Mice Carrying the Thr92Ala-DIO2 Polymorphism

Age Worsens the Cognitive Phenotype in Mice Carrying the Thr92Ala-DIO2 Polymorphism

The Monkey Head Mushroom and Memory Enhancement in Alzheimer’s Disease

Early Adversity and Accelerated Brain Aging: A Mini-Review

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