Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils

Zadali, Ramin; Ghareghozloo, Ebrahim Rostampour; Ramezani, Mohammad; Hassani, Vahid; Rafiei, Yasin; Chiyaneh, Shiva  Mohammadi; Meratan, Ali Akbar

doi:10.3791/59883

Cited by 4 publications

(2 citation statements)

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“…Similar impairments in the phospholipidic membrane were also noticed in PINK1+ patients even if those patients showed energetics impairments. This suggests that there might be a sort of connection between membrane deterioration and genetic mutations linked to PD and a potential link between phospholipidic membranes impairments and mitochondria function [42][43][44]. In this respect, further analyses are needed.…”

Section: Resting-state 31 P-mrsmentioning

confidence: 99%

In Vivo Mitochondrial Function in Idiopathic and Genetic Parkinson’s Disease

2019

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Parkinson's disease (PD) is associated with brain mitochondrial dysfunction. High-energy phosphates (HEPs), which rely on mitochondrial functioning, may be considered potential biomarkers for PD. Phosphorus magnetic resonance spectroscopy ( 31 P-MRS) is a suitable tool to explore in vivo cerebral energetics. We considered 10 31 P-MRS studies in order to highlight the main findings about brain energetic compounds in patients affected by idiopathic PD and genetic PD. The studies investigated several brain areas such as frontal lobes, occipital lobes, temporoparietal cortex, visual cortex, midbrain, and basal ganglia. Resting-state studies reported contrasting results showing decreased as well as normal or increased HEPs levels in PD patients. Functional studies revealed abnormal PCr + βATP levels in PD subjects during the recovery phase and abnormal values at rest, during activation and recovery in one PD subject with PINK1 gene mutation suggesting that mitochondrial machinery is more impaired in PD patients with PINK1 gene mutation. PD is characterized by energetics impairment both in idiopathic PD as well as in genetic PD, suggesting that mitochondrial dysfunction underlies the disease. Studies are still sparse and sometimes contrasting, maybe due to different methodological approaches. Further studies are needed to better assess the role of mitochondria in the PD development.

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Section: Resting-state 31 P-mrsmentioning

confidence: 99%

In Vivo Mitochondrial Function in Idiopathic and Genetic Parkinson’s Disease

2019

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“…Amyloidogenic peptides and proteins are soluble structures that are able to aggregate into insoluble amyloid fibrils with a characteristic core structure rich in β-sheets [1]. Evolutionary, these proteins have appeared in the microorganisms as necessary components of physiological functions such as biofilm formation [2], cell adhesion [3], interactions with host membranes [4], and permeabilization [5]. In humans, some of them also show physiological functions.…”

Section: Introductionmentioning

confidence: 99%

Curcumin Inhibits the Primary Nucleation of Amyloid-Beta Peptide: A Molecular Dynamics Study

et al. 2020

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The amyloid plaques are a key hallmark of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Amyloidogenesis is a complex long-lasting multiphase process starting with the formation of nuclei of amyloid peptides: a process assigned as a primary nucleation. Curcumin (CU) is a well-known inhibitor of the aggregation of amyloid-beta (Aβ) peptides. Even more, CU is able to disintegrate preformed Aβ firbils and amyloid plaques. Here, we simulate by molecular dynamics the primary nucleation process of 12 Aβ peptides and investigate the effects of CU on the process. We found that CU molecules intercalate among the Aβ chains and bind tightly to them by hydrogen bonds, hydrophobic, π–π, and cation–π interactions. In the presence of CU, the Aβ peptides form a primary nucleus of a bigger size. The peptide chains in the nucleus become less flexible and more disordered, and the number of non-native contacts and hydrogen bonds between them decreases. For comparison, the effects of the weaker Aβ inhibitor ferulic acid (FA) on the primary nucleation are also examined. Our study is in good agreement with the observation that taken regularly, CU is able to prevent or at least delay the onset of neurodegenerative disorders.

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Modulation of cytotoxic amyloid fibrillation and mitochondrial damage of α-synuclein by catechols mediated conformational changes

Zohoorian-Abootorabi

Meratan

Jafarkhani

et al. 2023

Sci Rep

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The interplay between α-synuclein (α-syn) and catechols plays a central role in Parkinson’s disease. This may be related to the modulating effects of catechols on the various aspects of α-syn fibrillization. Some of these effects may be attributed to the membrane-binding properties of the protein. In this work, we compare the effect of some catechols, including dopamine, epinephrine, DOPAL, and levodopa in micromolar concentrations, on the in vitro cytotoxicity of α-syn fibrils on human neuroblastoma SH-SY5Y cells. The study was followed by comparing the interactions of resulting structures with rat brain mitochondria used as an in vitro biological model. The obtained results demonstrate that catechols-induced structures have lost their cytotoxicity mimicking apoptotic cell death mediated by α-syn aggregates in different proportions. Moreover, α-syn fibrils-induced mitochondrial dysfunction, evaluated by a range of biochemical assays, was modulated by catechols-modified α-syn oligomers in different manners, as levodopa and DOPAL demonstrated the maximal and minimal effects, respectively. The plausible mechanism causing the inhibition of α-syn cytotoxic fibrillization and mitochondrial dysfunction by catechols is discussed. Taken together, we propose that catechols can prevent the cytotoxic assembly of α-syn and its destructive effects on mitochondria at various stages, suggesting that decreased levels of catechols in dopaminergic neurons might accelerate the α-syn cytotoxicity and mitochondrial dysfunction implicating Parkinson’s disease.

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Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils

Cited by 4 publications

References 0 publications

In Vivo Mitochondrial Function in Idiopathic and Genetic Parkinson’s Disease

In Vivo Mitochondrial Function in Idiopathic and Genetic Parkinson’s Disease

Curcumin Inhibits the Primary Nucleation of Amyloid-Beta Peptide: A Molecular Dynamics Study

Modulation of cytotoxic amyloid fibrillation and mitochondrial damage of α-synuclein by catechols mediated conformational changes

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