Nigral Neurons Degenerating in Parkinson's Disease Express the Angiotensin Receptor Type 1 Gene

Labandeira‐Garcia, Jose L.

doi:10.1002/mds.29137

Cited by 6 publications

(7 citation statements)

References 5 publications

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“…22 Interestingly, here, we identified that a natural compound derived from plantain seeds, PMS, could alleviate SN damage in PD mice by reducing microglia polarization. 10 We therefore thought that PMS could serve as a promising drug for PD treatment.…”

Section: ■ Resultsmentioning

confidence: 99%

“…Parkinson’s disease (PD) is known as a common neurodegenerative disease with major clinical manifestations of motor dysfunction, such as cognitive impairment. , PD usually occurs in people with the age of over 65 and is caused by the progressive degeneration of dopaminergic neurons in the substantia nigra (SN). − The cause of PD is still elusive. Previous studies have demonstrated that the pathogenesis of PD is related to aging factors, environmental factors, genetic factors, oxidative stress, free radical formation, and associated nerve inflammation, but recent evidence suggests that chronic nerve inflammation caused by microglia activation may be important in the degenerative process. , Activated microglia are a major factor in neuroinflammation and dopaminergic neurodegeneration. , Overactivation of microglia results in the release of several neurotoxic factors, which contributes to the process of dopaminergic neurodegeneration. , Therefore, inhibition of microglial activation may contribute to the treatment and prevention of PD. In addition, finding more drugs is needed to combat this disease.…”

Section: Introductionmentioning

confidence: 99%

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Plantamajoside Alleviates Substantia Nigra Damage in Parkinson’s Disease Mice by Inhibiting HDAC2/MAPK Signaling and Reducing Microglia Polarization

Guo

Chen

2023

ACS Chem. Neurosci.

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Parkinson’s disease (PD) is a common neurodegenerative disorder caused by dopaminergic neuron progressive degeneration. Inhibition of microglial activation may contribute to the treatment and prevention of PD. Plantamajoside (PMS) is a natural compound extracted from plantain seeds. It has a wide range of biological activities, including anti-inflammatory, antioxidative, as well as antitumor effects. However, its possible effects on PD are still unclear. In this study, lipopolysaccharide (LPS) was first injected into the right midbrain substantia nigra (SN) of male C57BL/6 mice to establish the PD mouse model. We found that PMS improved LPS-induced behavioral dysfunction in PD mice. PMS attenuated LPS-induced SN injury in PD mice. PMS could suppress LPS-induced microglial overactivation in PD mice. In addition, MS inhibited LPS-induced activation of the HDAC2/MAPK pathway in PD mice and BV-2 cells. It further revealed that PMS alleviated microglia polarization by inhibiting HDAC2. The limitation of this study was the lack of experiments for investigating the further molecular mechanism and in vivo animal validation, which needs to be further confirmed in the future. Collectively, our data suggested that PMS could serve as a promising drug for PD.

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Section: ■ Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Plantamajoside Alleviates Substantia Nigra Damage in Parkinson’s Disease Mice by Inhibiting HDAC2/MAPK Signaling and Reducing Microglia Polarization

Guo

Chen

2023

ACS Chem. Neurosci.

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“…Interestingly (Labandeira-Garcia and Parga, 2022), AT1 gene expression has been recently revealed as a major marker of dopaminergic neuron vulnerability in humans (Kamath et al, 2022). In rats, MetS also induced the increase in circulating levels of LIGHT and other major pro-inflammatory cytokines, together with an increase in 27-OHC levels.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies from our laboratory and others have involved the brain renin-angiotensin system (RAS) in progression of Parkinson's disease and other neurodegenerative diseases by enhancing neuronal oxidative stress and neuroinflammatory processes (Campos and Pacheco, 2020;Labandeira-Garcia et al, 2013;Labandeira-Garcia et al, 2017;Wright and Harding, 2019). Interestingly (Labandeira-Garcia and Parga, 2022), a recent study has shown that the population of human dopaminergic neurons most vulnerable to degeneration in Parkinson's disease can be identified by their high expression of angiotensin type-1 (AT1) gen (Kamath et al, 2022). Dysregulation of the tissue RAS also plays a major role in several of the above-mentioned components of the MetS.…”

Section: Introductionmentioning

confidence: 99%

AT1 receptor autoantibodies mediate effects of metabolic syndrome on dopaminergic vulnerability

Pedrosa¹,

Labandeira²,

Valenzuela³

et al. 2023

Brain, Behavior, and Immunity

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“…They act by antagonizing the angiotensin II (AT 1 ) receptor. It happens that this receptor, expressed in neurons, is a potential target of neurodegenerative diseases [83][84][85][86][87][88][89][90][91][92]. Animal models of neurodegenerative diseases have been instrumental in demonstrating that candesartan can cross the blood-brain barrier and act on receptors expressed in neural cells.…”

Section: Is It Good To Have Chronic Low Blood Pressure?mentioning

confidence: 99%

Can chronic therapeutic drug use by the elderly affect Alzheimer’s disease risk and rate of progression?

Franco

Serrano-Marín

2023

Explor Neuroprot Ther

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There is no approved drug capable of halting the progression of the most prevalent neurodegenerative disorders, namely Alzheimer’s disease (AD) and Parkinson’s disease (PD). Current therapeutic strategies focus mainly on the inhibition of the formation of protein aggregates and their deposition in the central nervous system. However, after almost a hundred years, proper management of the disease is still lacking. The fact of not finding effective management tools in the various clinical trials already carried out suggests that new hypotheses and strategies should be explored. Although vast resources have been allocated to the investigation of protein aggregates and the pathophysiology is now better understood, clues to the actual etiology are lacking. It is well known that brain homeostasis is of paramount importance for the survival of neurons. Drugs that target the periphery are often not subject to evaluation for their potential effect on the central nervous system. While acute treatments may be irrelevant, pills used for chronic conditions can be detrimental to neurons, especially in terms of progressive damage leading to a long-term decline in neuronal survival. Due to the lack of advances in the search for a curative treatment for neurodegenerative diseases, and the lack of new hypotheses about their etiology, a novel hypothesis is here proposed. It consists of assuming that the effects of the drugs most commonly used by the elderly, such as antihypertensive, hypoglycemic, and hypocholesterolemic, could have a negative impact on neuronal survival.

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Nigral Neurons Degenerating in Parkinson's Disease Express the Angiotensin Receptor Type 1 Gene

Abstract: © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Cited by 6 publications

References 5 publications

Plantamajoside Alleviates Substantia Nigra Damage in Parkinson’s Disease Mice by Inhibiting HDAC2/MAPK Signaling and Reducing Microglia Polarization

Plantamajoside Alleviates Substantia Nigra Damage in Parkinson’s Disease Mice by Inhibiting HDAC2/MAPK Signaling and Reducing Microglia Polarization

AT1 receptor autoantibodies mediate effects of metabolic syndrome on dopaminergic vulnerability

Can chronic therapeutic drug use by the elderly affect Alzheimer’s disease risk and rate of progression?

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