Telmisartan Ameliorates Astroglial and Dopaminergic Functions in a Mouse Model of Chronic Parkinsonism

Sathiya, S.; Mani, Sugumar; Barathidasan, R.; Manivasagam, Thamilarasan; Thenmozhi, Arokiasamy Justin; Bhat, Abid; Ray, Bipul; Essa, Musthafa Mohamed; Guillemin, Gilles J.; Chidambaram, Saravana Babu

doi:10.1007/s12640-018-9921-3

Cited by 17 publications

(8 citation statements)

References 44 publications

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“…A recent animal study showed that AT 1 and AT 2 form AT1/2 heterodimers, which are expressed in both striatal neurons and microglia in the central nervous system ( Rivas-Santisteban et al, 2020 ). Moreover, some experimental studies on the effects of telmisartan and candesartan, which are typical ARBs known to penetrate the BBB, showed an improvement in dopaminergic and mitochondrial functions in an animal PD model ( Sekar et al, 2018 ; Ray et al, 2021 ). Previous clinical studies on dementia also showed that BBB-crossing RAS inhibitors have better neuroprotective effects than non-BBB-crossing agents ( Ho et al, 2021 ; Ouk et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Renin-Angiotensin System Inhibitors on Parkinson’s Disease: A Nationwide Cohort Study

Kim

et al. 2022

Front. Pharmacol.

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Background: Renin-angiotensin system (RAS) inhibitors have been suggested as protective agents in Parkinson’s disease (PD). However, epidemiological evidence on the association between RAS inhibitors and the development of PD is inconsistent.Objectives: To investigate the effect of RAS inhibitors on PD risk in patients with ischemic heart disease (IHD) by type and cumulative duration of RAS inhibitors and their degree of blood-brain barrier (BBB) penetration ability.Methods: This was a propensity score-matched retrospective cohort study using 2008–2019 healthcare claims data from the Korean Health Insurance Review and Assessment database. The association between RAS inhibitor use and PD in patients with IHD was evaluated using multivariate Cox proportional hazard regression analysis. The risks are presented as adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).Results: Over a 10-year follow-up, 1,086 of 62,228 IHD patients developed PD. The Cox regression model showed that the use of RAS inhibitors was significantly associated with a lower risk of PD (aHR = 0.75; 95% CI 0.66–0.85) than the non-use of RAS inhibitors. Specifically, this reduced risk of PD only remained with the use of BBB-crossing angiotensin II receptor blockers (ARBs) (aHR = 0.62; 95% CI = 0.53–0.74), and this association was more definite with an increasing cumulative duration. A significantly reduced risk of PD was not observed with the use of BBB-crossing angiotensin-converting enzyme inhibitors.Conclusions: The use of ARBs with BBB-penetrating properties and a high cumulative duration significantly reduces the risk of PD in IHD patients. This protective effect could provide insight into disease-modifying drug candidates for PD.

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Section: Discussionmentioning

confidence: 99%

Protective Effect of Renin-Angiotensin System Inhibitors on Parkinson’s Disease: A Nationwide Cohort Study

Kim

et al. 2022

Front. Pharmacol.

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“…In contrast to curcumin supplementation in AD, which appears to provide no benefits to patients, our literature review has revealed some positive effects of curcumin supplementation in reducing several complications and symptoms of patients with PD. Deposition of α‐synuclein and Lewy bodies are PD's characteristics, as well as the progressive loss of dopaminergic neurons in the substantia nigra compacta (SNpc) (Mani, Sekar, Chidambaram, & Sevanan, 2018; Sekar et al, 2018). It has been found that the prodrug of the neurotoxin MPP+ (i.e., MPTP), which in experimental animal models destroys dopaminergic neurons in the substantia nigra and causes permanent symptoms of PD, is inhibited by curcumin, and consequently, dopaminergic neurons are protected from this neurotoxin (Harish et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

The clinical use of curcumin on neurological disorders: An updated systematic review of clinical trials

Mohseni

Sahebkar

Askari

et al. 2021

Phytotherapy Research

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Neuroprotective effects of curcumin have been shown in previous studies. This updated systematic review of clinical trials aimed to investigate the effect of curcumin on neurological disorders. Databases including PubMed, Scopus, Web of Science, and Google Scholar were systematically searched to identify clinical trials investigating the effects of curcumin/turmeric supplements alone, or in combination with other ingredients, on neurological diseases. Nineteen studies comprising 1,130 patients met the inclusion criteria. Generally, intervention and study outcomes were heterogeneous. In most of the studies, curcumin had a favorable effect on oxidative stress and inflammation. However, with the exception of AD, curcumin supplementation either alone, or in combination with other ingredients, had beneficial effects on clinical outcomes for the other aforementioned neurodegenerative diseases. For example, the frequency, severity, and duration of migraine attacks, scores on the revised ALS functional rating scale, and the occurrence of motor complications in PD were all significantly improved with curcumin supplementation either alone or in combination with other ingredients. However, in three studies, several adverse side effects (mostly gastrointestinal in nature) were reported. Curcumin supplementation may have favorable effects on inflammatory status and clinical outcomes of patients with neurological disease, although the results were not consistent.

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“…This was inhibited on treatment with selective antagonists to AT1 receptor [ 132 ]. RAS inhibitors, particularly AT1 receptor antagonists, attenuate dopaminergic degeneration in the MPTP-induced model of PD [ 133 ] ( Figure 3 ).…”

Section: Brain Rasmentioning

confidence: 99%

Mitochondria-Endoplasmic Reticulum Crosstalk in Parkinson’s Disease: The Role of Brain Renin Angiotensin System Components

et al. 2021

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The past few decades have seen an increased emphasis on the involvement of the mitochondrial-associated membrane (MAM) in various neurodegenerative diseases, particularly in Parkinson’s disease (PD) and Alzheimer’s disease (AD). In PD, alterations in mitochondria, endoplasmic reticulum (ER), and MAM functions affect the secretion and metabolism of proteins, causing an imbalance in calcium homeostasis and oxidative stress. These changes lead to alterations in the translocation of the MAM components, such as IP3R, VDAC, and MFN1 and 2, and consequently disrupt calcium homeostasis and cause misfolded proteins with impaired autophagy, distorted mitochondrial dynamics, and cell death. Various reports indicate the detrimental involvement of the brain renin–angiotensin system (RAS) in oxidative stress, neuroinflammation, and apoptosis in various neurodegenerative diseases. In this review, we attempted to update the reports (using various search engines, such as PubMed, SCOPUS, Elsevier, and Springer Nature) demonstrating the pathogenic interactions between the various proteins present in mitochondria, ER, and MAM with respect to Parkinson’s disease. We also made an attempt to speculate the possible involvement of RAS and its components, i.e., AT1 and AT2 receptors, angiotensinogen, in this crosstalk and PD pathology. The review also collates and provides updated information on the role of MAM in calcium signaling, oxidative stress, neuroinflammation, and apoptosis in PD.

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Telmisartan Ameliorates Astroglial and Dopaminergic Functions in a Mouse Model of Chronic Parkinsonism

Cited by 17 publications

References 44 publications

Protective Effect of Renin-Angiotensin System Inhibitors on Parkinson’s Disease: A Nationwide Cohort Study

Protective Effect of Renin-Angiotensin System Inhibitors on Parkinson’s Disease: A Nationwide Cohort Study

The clinical use of curcumin on neurological disorders: An updated systematic review of clinical trials

Mitochondria-Endoplasmic Reticulum Crosstalk in Parkinson’s Disease: The Role of Brain Renin Angiotensin System Components

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