A Potential Link Between Visceral Obesity and Risk of Alzheimer’s Disease

Al-Kuraishy, Hayder M; Al-Gareeb, Ali I; Alsayegh, Abdulrahman A.; Hakami, Zaki H.; Khamjan, Nizar A.; Saad, Hebatallah M.; Batiha, Gaber El‐Saber; Waard, Michel De

doi:10.1007/s11064-022-03817-4

Cited by 42 publications

(28 citation statements)

References 170 publications

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“…Parkinson's disease (PD) is the second most frequent neurodegenerative brain disease (NBD) after Alzheimer's disease (AD). 1 , 2 PD was primarily recognized in 1817 by Doctor James Parkinson who illustrates shaking palsy. 3 Of note, PD is developing due to dopaminergic neuron loss in the substantia nigra (SN) with subsequent dopamine deficiency in the caudate nucleus and putamen.…”

Section: Introductionmentioning

confidence: 99%

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Pros and cons for statins use and risk of Parkinson's disease: An updated perspective

Al-Kuraishy¹,

Al-Gareeb²,

Αλεξίου³

et al. 2023

Pharmacology Res & Perspec

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Parkinson's disease (PD) is the second most frequent neurodegenerative brain disease (NBD) after Alzheimer's disease (AD). Statins are the most common lipid‐lowering agents used in the management of dyslipidemia and the prevention of primary and secondary cardiovascular diseases (CVD) events. In addition, there is a controversial point regarding the role of serum lipids in the pathogenesis of PD. In this bargain, as statins reduce serum cholesterol so they affect the PD neuropathology in bidirectional ways either protective or harmful. Statins are not used in the management of PD, but they are frequently used in the cardiovascular disorders commonly associated with PD in the elderly population. Therefore, the use of statins in that population may affect PD outcomes. Concerning the potential role of statins on PD neuropathology, there are conflicts and controversies either protective against the development of PD or harmful by increasing the risk for the development of PD. Therefore, this review aimed to clarify the precise role of statins in PD regarding the pros and cons from published studies. Many studies suggest a protective role of statins against PD risk through the modulation of inflammatory and lysosomal signaling pathways. Nevertheless, other observations suggest that statin therapy may increase PD risk by diverse mechanisms including reduction of CoQ10. In conclusion, there are strong controversies regarding the protective role of statins in PD neuropathology. Therefore, retrospective and prospective studies are necessary in this regard.

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Section: Introductionmentioning

confidence: 99%

“…Parkinson's disease (PD) is the second most frequent neurodegenerative brain disease (NBD) after Alzheimer's disease (AD) 1,2 . PD was primarily recognized in 1817 by Doctor James Parkinson who illustrates shaking palsy 3 .…”

Section: Introductionmentioning

confidence: 99%

Pros and cons for statins use and risk of Parkinson's disease: An updated perspective

Al-Kuraishy¹,

Al-Gareeb²,

Αλεξίου³

et al. 2023

Pharmacology Res & Perspec

Self Cite

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“… 34 Therefore, NEP activity is positively correlated with IR and BMI in obese patients with cardiometabolic disorders. 23 , 34 …”

Section: Nep and Blood Glucose Homeostasismentioning

confidence: 99%

“…21 Aggregation of IAPP in the pancreas leads to the development of T2DM whereas accumulation of Aβ in the brain promotes the development of AD. 22,23 Therefore, both T2DM and AD share a similarity in the pathogenesis of brain IR and cognitive dysfunction. In this state, AD is classified as type 3 diabetes mellitus.…”

Section: Role Of Pancreatic Nep In T2dmmentioning

confidence: 99%

Effects of neprilysin and neprilysin inhibitors on glucose homeostasis: Controversial points and a promising arena

Alanazi

Al-Kuraishy

Al-Gareeb

et al. 2023

Journal of Diabetes

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Neprilysin (NEP) is a transmembrane zinc‐dependent metalloproteinase that inactivates various peptide hormones including glucagon‐like peptide 1 (GLP‐1). NEP inhibitors may be effective in the management of type 2 diabetes mellitus (T2DM) by increasing the circulating level of GLP‐1. However, acute‐effect NEP inhibitors may lead to detrimental effects by increasing blood glucose independent of GLP‐1. These findings suggest a controversial point regarding the potential role of NEP inhibitors on glucose homeostasis in T2DM patients. Therefore, this perspective aimed to clarify the controversial points concerning the role of NEP inhibitors on glucose homeostasis in T2DM. NEP inhibitors may lead to beneficial effects by inhibition of NEP, which is involved in the impairment of glucose homeostasis through modulation of insulin resistance. NEP increases dipeptidyl peptidase‐4 (DPP4) activity and contributes to increasing active GLP‐1 proteolysis so NEP inhibitors may improve glycemic control through increasing endogenous GLP‐1 activity and reduction of DPP4 activity. Thus, NEP inhibitors could be effective alone or in combination with antidiabetic agents in treating T2DM patients. However, long‐term and short‐term effects of NEP inhibitors may lead to a detrimental effect on insulin sensitivity and glucose homeostasis through different mechanisms including augmentation of substrates and pancreatic amyloid deposition. These findings are confirmed in animal but not in humans. In conclusion, NEP inhibitors produce beneficial rather than detrimental effects on glucose homeostasis and insulin sensitivity in humans though most of the detrimental effects of NEP inhibitors are confirmed in animal studies.

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“…Obesity is a risk factor for AD development as the increase in BMI affects some brain structures like cortical areas, and weight loss reverses brain atrophy, so authors refer to the “Obesity paradox” as a bias explained by reverse causation (Pegueroles et al 2018 ). In addition, visceral obesity favors AD development through tissue injury, oxidative stress, leptin resistance, inflammatory changes, glutamate excitotoxicity, and hypoadiponectinemia that collectively trigger neuroinflammation and amyloid β deposits (Lloret et al 2019 ; Al-Kuraishy et al 2022 ). Obesity animal models also support these pathological synergic findings; for example, diet-induced obesity in rodents can synergize with the TBI model by decreasing hippocampal plasticity and learning (Wu et al 2003 ).…”

Section: Generalities Of Microglial Cellsmentioning

confidence: 99%

Possible Implications of Obesity-Primed Microglia that Could Contribute to Stroke-Associated Damage

et al. 2023

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Microglia, the resident macrophages of the central nervous system, are essential players during physiological and pathological processes. Although they participate in synaptic pruning and maintenance of neuronal circuits, microglia are mainly studied by their activity modulating inflammatory environment and adapting their phenotype and mechanisms to insults detected in the brain parenchyma. Changes in microglial phenotypes are reflected in their morphology, membrane markers, and secreted substances, stimulating neighbor glia and leading their responses to control stimuli. Understanding how microglia react in various microenvironments, such as chronic inflammation, made it possible to establish therapeutic windows and identify synergic interactions with acute damage events like stroke. Obesity is a low-grade chronic inflammatory state that gradually affects the central nervous system, promoting neuroinflammation development. Obese patients have the worst prognosis when they suffer a cerebral infarction due to basal neuroinflammation, then obesity-induced neuroinflammation could promote the priming of microglial cells and favor its neurotoxic response, potentially worsening patients’ prognosis. This review discusses the main microglia findings in the obesity context during the course and resolution of cerebral infarction, involving the temporality of the phenotype changes and balance of pro- and anti-inflammatory responses, which is lost in the swollen brain of an obese subject. Graphical Abstract Obesity enhances proinflammatory responses during a stroke. Obesity-induced systemic inflammation promotes microglial M1 polarization and priming, which enhances stroke-associated damage, increasing M1 and decreasing M2 responses.

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A Potential Link Between Visceral Obesity and Risk of Alzheimer’s Disease

Cited by 42 publications

References 170 publications

Pros and cons for statins use and risk of Parkinson's disease: An updated perspective

Pros and cons for statins use and risk of Parkinson's disease: An updated perspective

Effects of neprilysin and neprilysin inhibitors on glucose homeostasis: Controversial points and a promising arena

Possible Implications of Obesity-Primed Microglia that Could Contribute to Stroke-Associated Damage

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