The Bewildering Effect of AMPK Activators in Alzheimer’s Disease: Review of the Current Evidence

Assefa, Brhane Teklebrhan; Tafere, Gebrehiwot Gebremedhin; Wondafrash, Dawit Zewdu; Gidey, Meles Tekie

doi:10.1155/2020/9895121

Cited by 34 publications

(19 citation statements)

References 225 publications

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“…This effect is relevant for cognition, since long-term memory requires new protein synthesis (Alberini, 2008). The effects of AMPK on amyloid β peptide accumulation, tau aggregation, and oxidative stress have been recently reviewed (Assefa et al, 2020). The role of AMPK in HD and ALS is discussed later in the appropriate sections.…”

Section: Amp-activated Protein Kinasementioning

confidence: 99%

Metabolic Aspects of Adenosine Functions in the Brain

et al. 2021

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Adenosine, acting both through G-protein coupled adenosine receptors and intracellularly, plays a complex role in multiple physiological and pathophysiological processes by modulating neuronal plasticity, astrocytic activity, learning and memory, motor function, feeding, control of sleep and aging. Adenosine is involved in stroke, epilepsy and neurodegenerative pathologies. Extracellular concentration of adenosine in the brain is tightly regulated. Adenosine may be generated intracellularly in the central nervous system from degradation of AMP or from the hydrolysis of S-adenosyl homocysteine, and then exit via bi-directional nucleoside transporters, or extracellularly by the metabolism of released nucleotides. Inactivation of extracellular adenosine occurs by transport into neurons or neighboring cells, followed by either phosphorylation to AMP by adenosine kinase or deamination to inosine by adenosine deaminase. Modulation of the nucleoside transporters or of the enzymatic activities involved in the metabolism of adenosine, by affecting the levels of this nucleoside and the activity of adenosine receptors, could have a role in the onset or the development of central nervous system disorders, and can also be target of drugs for their treatment. In this review, we focus on the contribution of 5′-nucleotidases, adenosine kinase, adenosine deaminase, AMP deaminase, AMP-activated protein kinase and nucleoside transporters in epilepsy, cognition, and neurodegenerative diseases with a particular attention on amyotrophic lateral sclerosis and Huntington’s disease. We include several examples of the involvement of components of the adenosine metabolism in learning and of the possible use of modulators of enzymes involved in adenosine metabolism or nucleoside transporters in the amelioration of cognition deficits.

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Section: Amp-activated Protein Kinasementioning

confidence: 99%

Metabolic Aspects of Adenosine Functions in the Brain

et al. 2021

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“…For AD, the effects of AMPK activators remain controversial. As reviewed recently by Assefa et al ( 2020 ), most AMPK activators evaluated in AD are indirect activators (such as resveratrol and metformin). In addition to AMPK, these compounds also have other targets important for neuronal functions and survival.…”

Section: Conclusion Remarksmentioning

confidence: 99%

Contribution of Energy Dysfunction to Impaired Protein Translation in Neurodegenerative Diseases

Liu

Chern

2021

Front. Cell. Neurosci.

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Impaired energy homeostasis and aberrant translational control have independently been implicated in the pathogenesis of neurodegenerative diseases. AMP kinase (AMPK), regulated by the ratio of cellular AMP and ATP, is a major gatekeeper for cellular energy homeostasis. Abnormal regulation of AMPK has been reported in several neurodegenerative diseases, including Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). Most importantly, AMPK activation is known to suppress the translational machinery by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1), activating translational regulators, and phosphorylating nuclear transporter factors. In this review, we describe recent findings on the emerging role of protein translation impairment caused by energy dysregulation in neurodegenerative diseases.

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“…AMPK plays a significant role in regulating the cell metabolism and energy status; and recent studies indicate that it may play a key role in AD (Assefa et al, 2020). Phosphorylation of AMPK at Thr( 172) is important for activation of the kinase (Stein et al, 2000).…”

Section: Central Inhibition Of Gipr Has a More Pronounced Impact On The Ampk Protein Level And Activitymentioning

confidence: 99%

Divergent effect of central incretin receptors inhibition in a rat model of sporadic Alzheimer’s disease

Barilar

Knezović

Homolak

et al. 2021

Preprint

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The incretin system is an emerging new field that might provide valuable contributions to the research of both pathophysiology and therapeutic strategies in the treatment of diabetes, obesity, and neurodegenerative disorders. This study aimed to explore the role of central glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) on cell metabolism and energy in the brain as well as on the levels of these incretins, insulin and glucose, by inhibiting the central incretins' receptors following intracerebroventricular administration of the respective antagonists in healthy rats and a streptozotocin-induced rat model of sporadic Alzheimer's disease (sAD). Chemical ablation of the central GIP receptor (GIPR) or GLP-1 receptor (GLP-1R) in healthy and diseased animals indicated a region-dependent role of incretins in the brain cell energy and metabolism and central incretin-dependent modulation of peripheral hormone secretion, markedly after GIPR inhibition, as well as a dysregulation of the GLP-1 system in experimental sAD.

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The Bewildering Effect of AMPK Activators in Alzheimer’s Disease: Review of the Current Evidence

Cited by 34 publications

References 225 publications

Metabolic Aspects of Adenosine Functions in the Brain

Metabolic Aspects of Adenosine Functions in the Brain

Contribution of Energy Dysfunction to Impaired Protein Translation in Neurodegenerative Diseases

Divergent effect of central incretin receptors inhibition in a rat model of sporadic Alzheimer’s disease

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