scholarly journals Targeting Mitochondria by Plant Secondary Metabolites: A Promising Strategy in Combating Parkinson’s Disease

2021 ◽  
Vol 22 (22) ◽  
pp. 12570
Author(s):  
Sajad Fakhri ◽  
Sadaf Abdian ◽  
Seyede Nazanin Zarneshan ◽  
Esra Küpeli Akkol ◽  
Mohammad Hosein Farzaei ◽  
...  

Parkinson’s disease (PD) is one of the most prevalent and debilitating neurodegenerative conditions, and is currently on the rise. Several dysregulated pathways are behind the pathogenesis of PD; however, the critical targets remain unclear. Accordingly, there is an urgent need to reveal the key dysregulated pathways in PD. Prevailing reports have highlighted the importance of mitochondrial and cross-talked mediators in neurological disorders, genetic changes, and related complications of PD. Multiple pathophysiological mechanisms of PD, as well as the low efficacy and side effects of conventional neuroprotective therapies, drive the need for finding novel alternative agents. Recently, much attention has been paid to using plant secondary metabolites (e.g., flavonoids/phenolic compounds, alkaloids, and terpenoids) in the modulation of PD-associated manifestations by targeting mitochondria. In this line, plant secondary metabolites have shown promising potential for the simultaneous modulation of mitochondrial apoptosis and reactive oxygen species. This review aimed to address mitochondria and multiple dysregulated pathways in PD by plant-derived secondary metabolites.

2019 ◽  
Vol 19 (7) ◽  
pp. 1022-1031 ◽  
Author(s):  
Paula D. Cebrián ◽  
Omar Cauli

Background: Many neurological disorders lead to institutionalization and can be accompanied in their advanced stages by functional impairment, and progressive loss of mobility, and cognitive alterations. Objective: We analyzed the relationship between functional impairment and cognitive performance and its related subdomains in individuals with Parkinson’s disease, Alzheimer’s disease accompanied by motor dysfunction, and with other neurological disorders characterized by both motor and cognitive problems. Methods: All participants lived in nursing homes (Valencia, Spain) and underwent cognitive evaluation with the Mini-Mental State Examination; functional assessment of independence in activities of daily living using the Barthel score and Katz index; and assessment of mobility with the elderly mobility scale. Results: The mean age of the subjects was 82.8 ± 0.6 years, 47% of the sample included individuals with Parkinson’s disease, and 48 % of the sample presented severe cognitive impairment. Direct significant relationships were found between the level of cognitive impairment and functional capacity (p < 0.01) and mobility (p < 0.05). Among the different domains, memory impairment was not associated with altered activities of daily living or mobility. The functional impairment and the risk of severe cognitive impairment were significantly (p<0.05) higher in female compared to male patients. Among comorbidities, overweight/obesity and diabetes were significantly (p < 0.05) associated with poor cognitive performance in those individuals with mild/moderate cognitive impairment. Conclusion: In institutionalized individuals with movement disorders there is an association between functional and cognitive impairment. Reduction of over-weight and proper control of diabetes may represent novel targets for improving cognitive function at such early stages.


2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Manan Binth Taj Noor ◽  
Nusrat Zerin Zenia ◽  
M Shamim Kaiser ◽  
Shamim Al Mamun ◽  
Mufti Mahmud

Abstract Neuroimaging, in particular magnetic resonance imaging (MRI), has been playing an important role in understanding brain functionalities and its disorders during the last couple of decades. These cutting-edge MRI scans, supported by high-performance computational tools and novel ML techniques, have opened up possibilities to unprecedentedly identify neurological disorders. However, similarities in disease phenotypes make it very difficult to detect such disorders accurately from the acquired neuroimaging data. This article critically examines and compares performances of the existing deep learning (DL)-based methods to detect neurological disorders—focusing on Alzheimer’s disease, Parkinson’s disease and schizophrenia—from MRI data acquired using different modalities including functional and structural MRI. The comparative performance analysis of various DL architectures across different disorders and imaging modalities suggests that the Convolutional Neural Network outperforms other methods in detecting neurological disorders. Towards the end, a number of current research challenges are indicated and some possible future research directions are provided.


2020 ◽  
Vol 35 (6) ◽  
pp. 871-871
Author(s):  
Ryan J ◽  
Kreiner D ◽  
Gontkovsky S ◽  
Paolo A

Abstract Objective Research has identified common genetic influences on handedness and neurological/mental health phenotypes. It also has been shown there may be increased risk for development of neurological disorders/diseases among individuals naturally left-handed or demonstrating non-right-hand preference. This investigation examined prevalence of right-handed versus non-right-handed individuals with Parkinson’s disease (PD) compared to controls. Method Participants were 264 patients with PD (mean age = 69.83 years) and 256 control volunteers (mean age = 71.42 years). Mean Dementia Rating Scale composites for the groups were 123.68 and 136.00, respectively. Participants self-identified their dominant hand for writing and usage was confirmed during the session. Results Proportions of non-right- and right-handed controls (7.0% and 93.0%) versus individuals with PD (6.8% and 93.2%) did not differ. Changes in proportions of non-right- and right-handedness across age ranges were not significant for controls or patients. There was a trend for a larger proportion of women (55.9%) versus men among controls (44.1%), □ 2 (1) = 3.29, p &lt; .10; whereas, the proportion of men (64.4%) with PD was larger than that of women. (35.6%), □ 2 (1) = 21.31, p &lt; .001. For controls and patients, non-right and right handedness gender proportions were similar. Conclusions This study is the first to assess handedness prevalence rates in PD. Results suggest prevalence of non-right handedness is similar in PD and healthy individuals and does not appear to differ markedly by gender or with advancing age. The occurrence of a trend for a larger proportion of women than men among controls is consistent with census-based statistics.


Author(s):  
Xin He ◽  
Yue Xie ◽  
Qiongping Zheng ◽  
Zeyu Zhang ◽  
Shanshan Ma ◽  
...  

Impairment of autophagy has been strongly implicated in the progressive loss of nigral dopaminergic neurons in Parkinson’s disease (PD). Transcription factor E3 (TFE3), an MiTF/TFE family transcription factor, has been identified as a master regulator of the genes that are associated with lysosomal biogenesis and autophagy. However, whether TFE3 is involved in parkinsonian neurodegeneration remains to be determined. In this study, we found decreased TFE3 expression in the nuclei of the dopaminergic neurons of postmortem human PD brains. Next, we demonstrated that TFE3 knockdown led to autophagy dysfunction and neurodegeneration of dopaminergic neurons in mice, implying that reduction of nuclear TFE3 may contribute to autophagy dysfunction-mediated cell death in PD. Further, we showed that enhancement of autophagy by TFE3 overexpression dramatically reversed autophagy downregulation and dopaminergic neurons loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. Taken together, these findings demonstrate that TFE3 plays an essential role in maintaining autophagy and the survival of dopaminergic neurons, suggesting TFE3 activation may serve as a promising strategy for PD therapy.


2021 ◽  
Vol 19 ◽  
Author(s):  
Tapan Behl ◽  
Gagandeep Kaur ◽  
Aayush Sehgal ◽  
Gokhan Zengin ◽  
Sukhbir Singh ◽  
...  

Background: Ionizing radiation from telluric sources is unceasingly an unprotected pitfall to humans. Thus, the foremost contributors to human exposure are global and medical radiations. Various pieces of evidences assembled during preceding years reveal the pertinent role of ionizing radiation-induced oxidative stress in the progression of neurodegenerative insults such as Parkinson’s disease, which have been contributing to increased proliferation and generation of reactive oxygen species. Objective: This review delineates the role of ionizing radiation-induced oxidative stress in Parkinson’s disease and proposes novel therapeutic interventions of flavonoid family offering effective management and slowing down the progression of Parkinson’s disease. Method: Published papers were searched via MEDLINE, PubMed, etc. published to date for in-depth database collection. Results: The potential of oxidative damage may harm the non-targeted cells. It can also modulate the functions of central nervous system, such as protein misfolding, mitochondria dysfunction, increased levels of oxidized lipids, and dopaminergic cell death, which accelerates the progression of Parkinson’s disease at the molecular, cellular, or tissue levels. In Parkinson’s disease, reactive oxygen species exacerbate the production of nitric oxides and superoxides by activated microglia, rendering death of dopaminergic neuronal cell through different mechanisms. Conclusion: Rising interest has extensively engrossed on the clinical trial designs based on the plant derived family of antioxidants. They are known to exert multifarious impact either way in neuroprotection via directly suppressing ionizing radiation-induced oxidative stress and reactive oxygen species production or indirectly increasing the dopamine levels and activating the glial cells.


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