Cellular function and pathological role of ATP13A2 and related P-type transport ATPases in Parkinson's disease and other neurological disorders

Введение. В настоящее время в научной литературе имеется большой объем данных, посвященных болезни Паркинсона. В то же время недостаточно освещена роль ренин-ангиотензиновой системы (РАС) в патогенезе заболевания. Цель - оценка современных патогенетически обоснованных подходов к терапии болезни Паркинсона. Методика. В базах данных Medline (PubMed) и eLibrary осуществлен подбор и анализ современных источников литературы, посвященных изучению роли ренин-ангиотензиновой системы в патогенезе болезни Паркинсона. Результаты. Болезнь Паркинсона является хроническим нейродегенеративным заболеванием, которое проявляется моторными и немоторными нарушениями. Анализ литературы показал, что помимо системной ренин-ангиотензиновой системы во многих тканях и органах имеется локальная РАС. Авторами было показано, что дофамин и ангиотензин II взаимодействуют в черной субстанции (SN) и стриатуме в реципрокном отношении. В модельных экспериментах на животных доказано, что снижение уровней дофамина сопровождается гиперактивацией ренин-ангиотензиновой системы. При этом так же отмечается выброс активных форм кислорода, индуцируемый микроглиальной тканью, и развитие нейровоспаления, что сопровождается нейродегенерацией. Применение блокаторов ангиотензиновых рецепторов в моделях на животных и в клинических испытаниях позволило значительно снизить прогрессирование нейродегенерации черной субстанции. Заключение. Авторами изложены результаты, свидетельствующие о том, что развитие болезни Паркинсона сопровождается гиперактивацией мозговой РАС. Подразумевается, что на новое звено патогенеза можно терапевтически воздействовать. Необходимы дополнительные исследования для понимания механизмов данных процессов. Background. A large amount of literature on Parkinson’s disease is currently available. However, the role of the renin-angiotensin system in the pathogenesis of this disease is not sufficiently covered. Aim. To highlight new therapeutic possibilities based on pathophysiological mechanisms of Parkinson’s disease. Methods. The literature retrieved from the PubMed, Medline, and eLibrary databases focusing on the role of the renin-angiotensin system in the pathogenesis of Parkinson’s disease was analyzed. Results. Parkinson’s disease (PD) is a chronic neurodegenerative disease associated with persistent neurological disorders. Studies have demonstrated that a local renin-angiotensin system (RAS) exists in many tissues and organs along with the systemic RAS. The authors showed that dopamine and angiotensin II interact reciprocally in the substantia nigra (SN) and striatum. In animal models, a decrease in the dopamine level was accompanied by RAS overactivation. Furthermore, microglial tissue induced production of reactive oxygen species, which was associated with neuroinflammation. The angiotensin receptor blocker treatment used in animal models and clinical trials significantly reduced the progression of SN neurodegeneration. Conclusions. The authors reviewed the data of literature demonstrating that the progression of Parkinson’s disease is associated with overactivation of the cerebral RAS. Apparently, it is possible to influence therapeutically this new pathogenetic component of Parkinson’s disease. Further study is required for understanding the mechanisms of this process.

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Analysing the role of Saraswatarishta in the treatment of neurological disorders based on network pharmacology

Neuroscience Research Notes ◽

10.31117/neuroscirn.v3i5.106 ◽

2021 ◽

Vol 3 (5) ◽

pp. 23-35

Author(s):

Vrinda Jethalia ◽

Sanjana Varada Hasyagar ◽

Kasturi Bhamidipati ◽

Jhinuk Chatterjee

Keyword(s):

Alzheimer’S Disease ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Parkinson's Disease ◽

Neurological Disorders ◽

Network Pharmacology ◽

Therapeutic Effects ◽

Target Disease ◽

Compound Target

Ayurvedic medications originated centuries ago and are still prevalent today. Saraswatarishta (SWRT) is a well-known ayurvedic formulation that is often prescribed to control the manifestations of neurological illnesses and disorders such as slurred speech, anxiety, Parkinson's disease (PD) and Alzheimer's disease(AD). However, scientific research on its mode of action has not been studied extensively. Therefore, this study employs network pharmacology to understand better the neuroprotective role of Saraswatarishta (SWRT) in neurological disorders. Out of the 18 ingredients in SWRT, five were considered in this study due to their elevated therapeutic action in neurological disorders. Further, nine active phytoconstituents were chosen from the five selected ingredients. The gene targets of the active phytoconstituents were screened and selected using STITCH, SwissTargetPrediction and ChEMBL. Protein-Protein interaction and Gene Ontology (GO) enrichment analysis were carried out using STRING and g:Profiler, respectively. Cytoscape 3.7.2 was used to create three networks-the compound-target, the target-disease and the compound-target-disease network. Molinspiration and admetSAR2.0 were used to obtain the bioactivity scores and the blood-brain barrier (BBB) probability scores. The three networks indicated that all nine phytoconstituents were linked to the gene targets that encode proteins involved in the pathways of 10 major neurological disorders. This includes Parkinson's disease (PD), Alzheimer's disease (AD), dementia, Huntington disease, epilepsy, schizophrenia, spinocerebellar ataxia, amyotrophic lateral sclerosis (ALS), multiple sclerosis and attention deficit hyperactivity disorder (ADHD). The gene targets were expressed significantly in various central nervous system regions such as the cerebral cortex, cerebellum and amygdala. The bioactivity scores of the phytoconstituents were in the active range along with high BBB probability scores, indicating that the phytoconstituents can potentially cross the BBB and impart therapeutic effects.

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The Effect of Magnesium Deficiency on Neurological Disorders: A Narrative Review Article

Iranian Journal of Public Health ◽

10.18502/ijph.v48i3.880 ◽

2019 ◽

Cited By ~ 1

Author(s):

Wenwen XUE ◽

Jing YOU ◽

Yingchao SU ◽

Qinglu WANG

Keyword(s):

Alzheimer’S Disease ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Parkinson's Disease ◽

Cerebral Vasospasm ◽

Neurological Disorders ◽

Essential Element ◽

The Body ◽

Mg Deficiency

Background: Magnesium (Mg) is an essential element for the body. It is a cofactor for ATP, DNA, and RNA and more than 600 enzymes. As it is similar to Ca2+, this element can also act as a cell signaling molecule and play multiple important roles in the nervous, muscle, and immune systems. Recent studies have associated Mg-deficiency with many neurological disorders, such as cerebral vasospasm, Alzheimer’s disease, stroke, and migraine. As it plays such a crucial role in human body, therefore, we summarized the role of Mg in neurological disorders to illustrate the symptoms caused by Mg-deficiency and the possible underlying mechanisms. Methods: We critically discuss the role of it that we review the recent literature of magnesium. We also review the available data which are concerning the role of magnesium in neurological disorders. Results: Magnesium is related to neurological disorders on the basis of the study of animals and humans experiments. Furthermore, these nervous systems related diseases include cerebral vasospasm, Alzheimer’s disease, Parkinson’s disease, stroke and migraine. Conclusion: Magnesium has effects on neurological disorders, such as its utility in cerebral vasospasm, Alzheimer’s disease, Parkinson’s disease, stroke and migraine. So here we make a brief review to conclude it.

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