Benzodiazepines in Alzheimer’s disease: beneficial or detrimental effects

Al-Kuraishy, Hayder M; Al-Gareeb, Ali I; Saad, Hebatallah M.; Batiha, Gaber El‐Saber

doi:10.1007/s10787-022-01099-4

Cited by 32 publications

(33 citation statements)

References 94 publications

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“…Together, these data indicate that a reduction in neuron‐derived cholesterol content, similar to that observed in the diabetic brain, creates a state of insulin and growth factor resistance that could contribute to CNS‐related complications of diabetes, including increased risk of neurodegenerative diseases, such as AD 71 . However, statins improve rather than reduce cognitive function in AD patients 18,72 . Notably, lipophilic statins lead to a more detrimental effect on PD neuropathology 27 .…”

Section: Harmful Role Of Statins In Pdmentioning

confidence: 87%

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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: Harmful Role Of Statins In Pdmentioning

confidence: 87%

“… 71 However, statins improve rather than reduce cognitive function in AD patients. 18 , 72 Notably, lipophilic statins lead to a more detrimental effect on PD neuropathology. 27 The detrimental effect of statins on PD neuropathology is through direct effects on the neurons rather than by reducing serum cholesterol.…”

Section: Harmful Role Of Statins In Pdmentioning

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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“…In this state, AD is classified as type 3 diabetes mellitus. 22 , 24 IAPP is derived from pre‐pro‐IAPP to form 37 amino acid peptide. 25 Notably, IAPP is co‐secreted with insulin from pancreatic β cells into circulation.…”

Section: Role Of Pancreatic Nep In T2dmmentioning

confidence: 99%

“…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 22,24 . IAPP is derived from pre‐pro‐IAPP to form 37 amino acid peptide 25 .…”

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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“…Of note, advanced glycation end‐products (AGEs) are implicated in the pathogenesis of acute and chronic inflammation and aging‐related atherosclerosis. [ 129–133 ] AGEs are typically produced during the aging process, though excessive production of AGEs is associated with vascular inflammation, atherosclerosis, OS, insulin resistance, and diabetes. [ 134 ] AGEs promote the release of pro‐inflammatory cytokines in diabetes and other metabolic disorders.…”

Section: Nrf2 Role In Inflammation and Immune Responsementioning

confidence: 99%

The possible role of nuclear factor erythroid‐2‐related factor 2 activators in the management of Covid‐19

Al‐kuraishy,

Al‐Gareeb,

Eldahshan

et al. 2023

J Biochem & Molecular Tox

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COVID‐19 is caused by a novel SARS‐CoV‐2 leading to pulmonary and extra‐pulmonary manifestations due to oxidative stress (OS) development and hyperinflammation. COVID‐19 is primarily asymptomatic though it may cause acute lung injury (ALI), acute respiratory distress syndrome (ARDS), systemic inflammation, and thrombotic events in severe cases. SARS‐CoV‐2‐induced OS triggers the activation of different signaling pathways, which counterbalances this complication. One of these pathways is nuclear factor erythroid 2‐related factor 2 (Nrf2), which induces a series of cellular interactions to mitigate SARS‐CoV‐2‐mediated viral toxicity and OS‐induced cellular injury. Nrf2 pathway inhibits the expression of pro‐inflammatory cytokines and the development of cytokine storm in COVID‐19. Therefore, Nrf2 activators may play an essential role in reducing SARS‐CoV‐2 infection‐induced inflammation by suppressing NLRP3 inflammasome in COVID‐19. Furthermore, Nrf2 activators can attenuate endothelial dysfunction (ED), renin‐angiotensin system (RAS) dysregulation, immune thrombosis, and coagulopathy. Thus this mini‐review tries to clarify the possible role of the Nrf2 activators in the management of COVID‐19. Nrf2 activators could be an effective therapeutic strategy in the management of Covid‐19. Preclinical and clinical studies are recommended in this regard.

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Benzodiazepines in Alzheimer’s disease: beneficial or detrimental effects

Cited by 32 publications

References 94 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

The possible role of nuclear factor erythroid‐2‐related factor 2 activators in the management of Covid‐19

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