Shared signaling pathways in Alzheimer’s and metabolic disease may point to new treatment approaches

Suresh, Jahnavi; Khor, Ing Wei; Kaur, Prameet; Heng, Hui Li; Torta, Federico; Dawe, Gavin S.; Tai, E Shyong; Tolwinski, Nicholas S.

doi:10.1111/febs.15540

Cited by 22 publications

(16 citation statements)

References 204 publications

(236 reference statements)

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“…AD has been extensively characterized by the gradual decline of neuronal health. Neurotoxins, TAU protein neurofibrillary tangles, amyloid-beta (Aβ) plaque accumulation in mature neuron phenotypes [1][2][3][4][5], mitochondria dysfunction (fusion-fission imbalance) [6,7], and neuroinflammation collectively involves in neurodegeneration in AD [8][9][10][11]. Mitochondrial dysfunction results in the accumulation of harmful reactive oxygen species (ROS), which subsequently trigger CNS apoptotic decline [7].…”

Section: Introductionmentioning

confidence: 99%

The Potential Role of Cytokines and Growth Factors in the Pathogenesis of Alzheimer’s Disease

Ogunmokun,

Dewanjee,

Chakraborty

et al. 2021

Cells

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Alzheimer’s disease (AD) is one of the most prominent neurodegenerative diseases, which impairs cognitive function in afflicted individuals. AD results in gradual decay of neuronal function as a consequence of diverse degenerating events. Several neuroimmune players (such as cytokines and growth factors that are key players in maintaining CNS homeostasis) turn aberrant during crosstalk between the innate and adaptive immunities. This aberrance underlies neuroinflammation and drives neuronal cells toward apoptotic decline. Neuroinflammation involves microglial activation and has been shown to exacerbate AD. This review attempted to elucidate the role of cytokines, growth factors, and associated mechanisms implicated in the course of AD, especially with neuroinflammation. We also evaluated the propensities and specific mechanism(s) of cytokines and growth factors impacting neuron upon apoptotic decline and further shed light on the availability and accessibility of cytokines across the blood-brain barrier and choroid plexus in AD pathophysiology. The pathogenic and the protective roles of macrophage migration and inhibitory factors, neurotrophic factors, hematopoietic-related growth factors, TAU phosphorylation, advanced glycation end products, complement system, and glial cells in AD and neuropsychiatric pathology were also discussed. Taken together, the emerging roles of these factors in AD pathology emphasize the importance of building novel strategies for an effective therapeutic/neuropsychiatric management of AD in clinics.

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Section: Introductionmentioning

confidence: 99%

The Potential Role of Cytokines and Growth Factors in the Pathogenesis of Alzheimer’s Disease

Ogunmokun,

Dewanjee,

Chakraborty

et al. 2021

Cells

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“…This cluster was enriched for processes associated with autophagy, lysosomal activity (Supplemental Figure S2), and the regulation of signaling pathways whose activation has previously been found to be protective against AD, e.g. EGFR, FoxO, and mTOR (ODDO 2012;CAI et al 2015;SURESH et al 2020). Cluster III (N = 785) and Cluster IV (N = 630) consisted of genes that were Wnt-repressed or Wnt-activated respectively, i.e.…”

Section: Resultsmentioning

confidence: 99%

“…In an update to our previously published study, we followed up on a comment made by one of the referees, namely which mechanism does Lithium use to extend the lifespan of Drosophila expressing Ab 1-42 -CRY2-mCh. We postulated that the Wnt pathway was the key component to this based on previous studies (NG et al 2019;SURESH et al 2020). However, we were unable to test the model in embryonic neurogenesis as application of Lithium and Wnt to embryos proved either technically or genetically problematic, and instead we investigated this in the Drosophila gut, an adult homeostasis model.…”

Section: Discussionmentioning

confidence: 99%

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Wnt signaling rescues amyloid beta induced stem cell loss

Kaur

Chua

Lim

et al. 2021

Preprint

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Previously, we established an optogenetic model to induce Amyloid-β intracellular oligomerization to model distinct disease etiologies (Lim et al. 2020). Here we examine the effect of Wnt signaling on Amyloid in this model. We observe that Wnt activation rescues the detrimental effects of Amyloid expression and oligomerization. We analyze the gene expression changes downstream of Wnt that contribute to this rescue and find changes in aging related genes, protein misfolding, metabolism and inflammation. We propose that Wnt expression reduces inflammation through repression of Toll activating factors and confirm that chronic Toll activation reduces lifespan. We propose that the protective effect observed for Lithium treatment functions at least in part through Wnt activation and inhibition of inflammation.

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“…Levels of human amylin cause different extents of oligomerization, which correspond to diabetes disease stages. Diabetes phenotypes differ according to amylin overproduction levels [ 144 ], and there are similarities between Type 2 diabetes and Alzheimer’s disease [ 145 ]. The toxicity of amylin fibrils is similar to the toxicity of Amyloid-β proteins in Alzheimer’s disease [ 143 ].…”

Section: Optogenetic Approachesmentioning

confidence: 99%

Optogenetic approaches for understanding homeostatic and degenerative processes in Drosophila

Lim

Kaur

Huang

et al. 2021

Cell. Mol. Life Sci.

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Many organs and tissues have an intrinsic ability to regenerate from a dedicated, tissue-specific stem cell pool. As organisms age, the process of self-regulation or homeostasis begins to slow down with fewer stem cells available for tissue repair. Tissues become more fragile and organs less efficient. This slowdown of homeostatic processes leads to the development of cellular and neurodegenerative diseases. In this review, we highlight the recent use and future potential of optogenetic approaches to study homeostasis. Optogenetics uses photosensitive molecules and genetic engineering to modulate cellular activity in vivo , allowing precise experiments with spatiotemporal control. We look at applications of this technology for understanding the mechanisms governing homeostasis and degeneration as applied to widely used model organisms, such as Drosophila melanogaster , where other common tools are less effective or unavailable.

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Shared signaling pathways in Alzheimer’s and metabolic disease may point to new treatment approaches

Cited by 22 publications

References 204 publications

The Potential Role of Cytokines and Growth Factors in the Pathogenesis of Alzheimer’s Disease

The Potential Role of Cytokines and Growth Factors in the Pathogenesis of Alzheimer’s Disease

Wnt signaling rescues amyloid beta induced stem cell loss

Optogenetic approaches for understanding homeostatic and degenerative processes in Drosophila

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