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Neurodegenerative disorders and osteoporosis share some common underlying pathological features including calcium overload, accumulation of toxic chemicals, inflammation and impaired protein prenylation by isoprenoids (farnesyl pyrophosphate and geranylgeranyl pyrophosphate) appear later stage of life. Substantial number of pre-clinical and clinical reports as well as in vitro data univocally acknowledged the negative impact of altered post-translational modification (prenylation) of proteins like small GTPases (Rffhes, Rho, Rac etc.) and cholesterol levels in both serum and brain on CNS integrity. Bisphosphonates (BPs), referred to as gold standard for osteoporosis treatment, have well established role in attenuation of bone resorption and osteoclast apoptosis by inhibition of farnesyl pyrophosphate synthase enzyme (FPPS) in mevalonate pathway. BPs mainly nitrogen containing BPs (NBPs) have potential to offer new therapeutic targets for neurological disorders and received increasing attention in recent years. A year back clinical and pre-clinical studies revealed that NBPs have the potential to alleviate the symptoms of neurological disorders like brain calcification, Alzheimer's disease and Huntington's disease by targeting mevalonate pathway. Though these drugs have well developed role in inhibition of isoprenoids synthesis, these were demonstrated to inhibit acetyl cholinesterase enzyme and cholesterol synthesis in brain that are considered as the critical factors for impairment of cognitive functions which is the hallmark of several neurological disorders. Still the current understanding of BPs' effect in CNS is limited due to lack of studies focusing the molecular and cellular mechanism. The present review aims to reveal the updated discussion on the mechanism contributing BPs' effect in CNS disorders.

Large populations are the sufferers of the neurological disorders, pointing the need for investigation of such therapeutic interventions which target and delay the underlying pathological hallmarks and exert positive influence on different neurological health problems. Hypolipidemic, hypoglycemic, antioxidant, and immunomodulatory effects of fenugreek and its constituents with their potential role in various neurological disorders were already reported. In future, it would be of even greater interest to further develop more effective dosage, supplementation period, and to evaluate the therapeutic potentials of fenugreek and its constituents in neurological disorders by exploring underlying cellular and molecular mechanisms.

Background and AimA growing body of literature suggests the association between dementia risk and proton pump inhibitor (PPI) use. Therefore, we aimed to investigate the association between PPI use and dementia risk.MethodsAn extensive literature search was performed in PubMed, Embase, and Cochrane till March 31, 2019. All the studies (cohort and case–control) assessing the association between PPI use and dementia risk were eligible for inclusion. Articles were selected based on the screening of title and abstract, data were extracted, and risk of bias was assessed using Newcastle–Ottawa scale. The primary outcome was pooled risk of dementia among PPI user as compared with non‐PPI user. Secondary outcomes include dementia risk based on subgroups. Statistical analysis was performed using review manager software.ResultsTwelve studies (eight cohort and four case–control) were found to be eligible for inclusion. Majority of the studies were of high quality. Dementia was diagnosed based on International Classification of Diseases 9/10 codes in majority of the included studies. PPI use was not associated with the dementia risk, with a pooled relative risk (RR) of 1.05 (95% confidence interval [CI]: 0.96–1.15), P = 0.31. Subgroup analysis based on study design (cohort: P = 0.14; case–control: P = 0.14), sex (RR 1.25 [95% CI: 0.97–1.60], P = 0.08), histamine 2 receptor antagonist blockers (P = 0.93), and Alzheimer's disease (RR 1.00 [95% CI: 0.91–1.09], P = 0.93) revealed no significant association between PPI use and dementia risk.ConclusionWe found no significant association between PPI use and the risk of dementia or Alzheimer's disease.

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