Genetic polymorphisms in the renin-angiotensin system and cognitive decline in Parkinson’s disease

Pierzchlińska, Anna; Sławek, Jarosław; Mak, Monika; Gawrońska-Szklarz, B; Białecka, Monika

doi:10.1007/s11033-021-06569-6

Cited by 6 publications

(5 citation statements)

References 48 publications

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“… 90 However, a cohort study on 256 PD patients showed no significant association between single nucleotide polymorphisms (SNPs) of RAS components with PD risk and cognitive impairment. 91 Though, these SNPs of RAS may affect the response and therapeutic efficacy of ACEIs and ARBs in PD patients. A meta‐analysis establish no significant connotation between ACE gene PD risks.…”

Section: Role Of Ras In Pdmentioning

confidence: 99%

“…A case–control study on 127 PD patients and 198 healthy controls showed that homozygote DD genotype of ACE gene was higher in PD patients compared to healthy controls 90 . However, a cohort study on 256 PD patients showed no significant association between single nucleotide polymorphisms (SNPs) of RAS components with PD risk and cognitive impairment 91 . Though, these SNPs of RAS may affect the response and therapeutic efficacy of ACEIs and ARBs in PD patients.…”

Section: Role Of Ras In Pdmentioning

confidence: 99%

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The potential role of brain renin‐angiotensin system in the neuropathology of Parkinson disease: Friend, foe or turncoat?

Al‐Qahtani,

Al‐kuraishy,

Al‐Gareeb

et al. 2024

J Cellular Molecular Medi

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Parkinson disease (PD) is one of the most common neurodegenerative diseases of the brain. Of note, brain renin‐angiotensin system (RAS) is intricate in the PD neuropathology through modulation of oxidative stress, mitochondrial dysfunction and neuroinflammation. Therefore, modulation of brain RAS by angiotensin receptor blockers (ARBs) and angiotensin‐converting enzyme inhibitors (ACEIs) may be effective in reducing the risk and PD neuropathology. It has been shown that all components including the peptides and enzymes of the RAS are present in the different brain areas. Brain RAS plays a critical role in the regulation of memory and cognitive function, and in the controlling of central blood pressure. However, exaggerated brain RAS is implicated in the pathogenesis of different neurodegenerative diseases including PD. Two well‐known pathways of brain RAS are recognized including; the classical pathway which is mainly mediated by AngII/AT1R has detrimental effects. Conversely, the non‐classical pathway which is mostly mediated by ACE2/Ang1‐7/MASR and AngII/AT2R has beneficial effects against PD neuropathology. Exaggerated brain RAS affects the viability of dopaminergic neurons. However, the fundamental mechanism of brain RAS in PD neuropathology was not fully elucidated. Consequently, the purpose of this review is to disclose the mechanistic role of RAS in in the pathogenesis of PD. In addition, we try to revise how the ACEIs and ARBs can be developed for therapeutics in PD.

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Section: Role Of Ras In Pdmentioning

confidence: 99%

Section: Role Of Ras In Pdmentioning

confidence: 99%

The potential role of brain renin‐angiotensin system in the neuropathology of Parkinson disease: Friend, foe or turncoat?

Al‐Qahtani,

Al‐kuraishy,

Al‐Gareeb

et al. 2024

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…RAS downregulation via ACE inhibitors or AT1R blockers has shown protective effects against cognitive impairment [ 140 ]. A recent clinical study found no associations between cognitive decline in PD and specific single nucleotide polymorphisms (SNPs) in genes encoding angiotensinogen, ATR1, ATR2, and ACE [ 141 ]. Furthermore, NLRP3 inflammasome gene variants have been associated with critical disease in COVID-19 patients, especially in men and older patients, as well as patients with diabetes type 2, hypertension, and a higher body mass index [ 142 ].…”

Section: Future Perspectivesmentioning

confidence: 99%

Exploring the Role of ACE2 as a Connecting Link between COVID-19 and Parkinson’s Disease

Angelopoulou

Karlafti

Georgakopoulou

et al. 2023

Life

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Coronavirus disease 2019 (COVID-19) is frequently accompanied by neurological manifestations such as headache, delirium, and epileptic seizures, whereas ageusia and anosmia may appear before respiratory symptoms. Among the various neurological COVID-19-related comorbidities, Parkinson’s disease (PD) has gained increasing attention. Some cases of PD disease have been linked to COVID-19, and both motor and non-motor symptoms in Parkinson’s disease patients frequently worsen following SARS-CoV-2 infection. Although it is still unclear whether PD increases the susceptibility to SARS-CoV-2 infection or whether COVID-19 increases the risk of or unmasks future cases of PD, emerging evidence sheds more light on the molecular mechanisms underlying the relationship between these two diseases. Among them, angiotensin-converting enzyme 2 (ACE2), a significant component of the renin-angiotensin system (RAS), seems to play a pivotal role. ACE2 is required for the entry of SARS-CoV-2 to the human host cells, and ACE2 dysregulation is implicated in the severity of COVID-19-related acute respiratory distress syndrome (ARDS). ACE2 imbalance is implicated in core shared pathophysiological mechanisms between PD and COVID-19, including aberrant inflammatory responses, oxidative stress, mitochondrial dysfunction, and immune dysregulation. ACE2 may also be implicated in alpha-synuclein-induced dopaminergic degeneration, gut–brain axis dysregulation, blood–brain axis disruption, autonomic dysfunction, depression, anxiety, and hyposmia, which are key features of PD.

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“…(1) Receptor D1 . Whereas various investigations have failed to see any bipolar changes in the D1 receptor gene [ 71 , 72 ], a connection between polymorphism of the D1 receptor A48G and bipolar disease has been observed [ 73 , 74 ].…”

Section: Gpcrs and Mood Disordersmentioning

confidence: 99%

Insights into the Promising Prospect of G Protein and GPCR-Mediated Signaling in Neuropathophysiology and Its Therapeutic Regulation

Rahman

Islam

Mim

et al. 2022

Oxidative Medicine and Cellular Longevity

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G protein-coupled receptors (GPCRs) are intricately involved in the conversion of extracellular feedback to intracellular responses. These specialized receptors possess a crucial role in neurological and psychiatric disorders. Most nonsensory GPCRs are active in almost 90% of complex brain functions. At the time of receptor phosphorylation, a GPCR pathway is essentially activated through a G protein signaling mechanism via a G protein-coupled receptor kinase (GRK). Dopamine, an important neurotransmitter, is primarily involved in the pathophysiology of several CNS disorders; for instance, bipolar disorder, schizophrenia, Parkinson’s disease, and ADHD. Since dopamine, acetylcholine, and glutamate are potent neuropharmacological targets, dopamine itself has potential therapeutic effects in several CNS disorders. GPCRs essentially regulate brain functions by modulating downstream signaling pathways. GPR6, GPR52, and GPR8 are termed orphan GPCRs because they colocalize with dopamine D1 and D2 receptors in neurons of the basal ganglia, either alone or with both receptors. Among the orphan GPCRs, the GPR52 is recognized for being an effective psychiatric receptor. Various antipsychotics like aripiprazole and quetiapine mainly target GPCRs to exert their actions. One of the most important parts of signal transduction is the regulation of G protein signaling (RGS). These substances inhibit the activation of the G protein that initiates GPCR signaling. Developing a combination of RGS inhibitors with GPCR agonists may prove to have promising therapeutic potential. Indeed, several recent studies have suggested that GPCRs represent potentially valuable therapeutic targets for various psychiatric disorders. Molecular biology and genetically modified animal model studies recommend that these enriched GPCRs may also act as potential therapeutic psychoreceptors. Neurotransmitter and neuropeptide GPCR malfunction in the frontal cortex and limbic-related regions, including the hippocampus, hypothalamus, and brainstem, is likely responsible for the complex clinical picture that includes cognitive, perceptual, emotional, and motor symptoms. G protein and GPCR-mediated signaling play a critical role in developing new treatment options for mental health issues, and this study is aimed at offering a thorough picture of that involvement. For patients who are resistant to current therapies, the development of new drugs that target GPCR signaling cascades remains an interesting possibility. These discoveries might serve as a fresh foundation for the creation of creative methods for pharmacologically useful modulation of GPCR function.

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Genetic polymorphisms in the renin-angiotensin system and cognitive decline in Parkinson’s disease

Cited by 6 publications

References 48 publications

The potential role of brain renin‐angiotensin system in the neuropathology of Parkinson disease: Friend, foe or turncoat?

The potential role of brain renin‐angiotensin system in the neuropathology of Parkinson disease: Friend, foe or turncoat?

Exploring the Role of ACE2 as a Connecting Link between COVID-19 and Parkinson’s Disease

Insights into the Promising Prospect of G Protein and GPCR-Mediated Signaling in Neuropathophysiology and Its Therapeutic Regulation

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