Common Mechanisms Underlying α-Synuclein-Induced Mitochondrial Dysfunction in Parkinson’s Disease

Sohrabi, Tahereh; Mirzaei-Behbahani, Behnaz; Zadali, Ramin; Pirhaghi, Mitra; Morozova‐Roche, Ludmilla A.; Meratan, Ali Akbar

doi:10.1016/j.jmb.2023.167992

Cited by 22 publications

(14 citation statements)

References 225 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PD is a progressive neurodegenerative disease that affects 2–3% of individuals, aged 65 and older. It is the second most prevalent neurodegenerative disease, following AD, characterized by the presence of abnormal forms of α-Syn, a protein predominantly expressed in neurons of the central and peripheral nervous system. − In PD, α-Syn undergoes a pathological change, adopting a β-sheet structure that recruits more monomers, leading to the formation of oligomers and amyloid fibrils. This pathological transformation triggers progressive neuronal death by contributing to mitochondrial dysfunction, lysosomal impairment, and disruption of calcium homeostasis .…”

Section: Application Of Cpps To Prevent Neuronal Degenerationmentioning

confidence: 99%

“…Mitochondria are both the target of ROS damage and the site of ROS production, making them a crucial factor in the development of PD. 195 To prevent or reduce PD, it is important to deliver antioxidants directly to the mitochondria. Kang et al developed a mitochondrial targeting peptide (CAMP; human cathelicidin antimicrobial peptide) with cell-penetrating activity that was successfully coupled to the antioxidant protein human metallothionein 1a (hMT1A) and delivered to mitochondria.…”

Section: Brain Delivery and Cell Membrane Penetration Of Drugsmentioning

confidence: 99%

“…PD is also linked to the excessive accumulation of reactive oxygen species (ROS), which leads to oxidative stress. Mitochondria are both the target of ROS damage and the site of ROS production, making them a crucial factor in the development of PD . To prevent or reduce PD, it is important to deliver antioxidants directly to the mitochondria.…”

Section: Application Of Cpps To Prevent Neuronal Degenerationmentioning

confidence: 99%

See 2 more Smart Citations

Cell-Penetrating Peptides: Promising Therapeutics and Drug-Delivery Systems for Neurodegenerative Diseases

Pirhaghi,

Mamashli,

Moosavi-Movahedi

et al. 2024

Mol. Pharmaceutics

Self Cite

View full text Add to dashboard Cite

Currently, one of the most significant and rapidly growing unmet medical challenges is the treatment of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). This challenge encompasses the imperative development of efficacious therapeutic agents and overcoming the intricacies of the blood−brain barrier for successful drug delivery. Here we focus on the delivery aspect with particular emphasis on cell-penetrating peptides (CPPs), widely used in basic and translational research as they enhance drug delivery to challenging targets such as tissue and cellular compartments and thus increase therapeutic efficacy. The combination of CPPs with nanomaterials such as nanoparticles (NPs) improves the performance, accuracy, and stability of drug delivery and enables higher drug loads. Our review presents and discusses research that utilizes CPPs, either alone or in conjugation with NPs, to mitigate the pathogenic effects of neurodegenerative diseases with particular reference to AD and PD.

show abstract

Section: Application Of Cpps To Prevent Neuronal Degenerationmentioning

confidence: 99%

Section: Brain Delivery and Cell Membrane Penetration Of Drugsmentioning

confidence: 99%

Section: Application Of Cpps To Prevent Neuronal Degenerationmentioning

confidence: 99%

See 1 more Smart Citation

Cell-Penetrating Peptides: Promising Therapeutics and Drug-Delivery Systems for Neurodegenerative Diseases

Pirhaghi,

Mamashli,

Moosavi-Movahedi

et al. 2024

Mol. Pharmaceutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…In this respect, α-synuclein-associated mutations, for instance, in the SNCA gene, are related not only with familial PD but also predispose to sporadic disease. Pathological mechanisms that also contribute in PD evolution are mitochondrial dysfunction, the production of reactive oxygen species and other oxidative species, defective calcium homeostasis, endoplasmic reticulum/Golgi impairment, and microglia activation in the context of neuroinflammation [ 113 ]. Apart from the motor dysfunction in PD, non-motor symptoms have been the focus of extensive research, such as impairment of olfaction, mood disorders, and cognitive deficit [ 114 , 115 ].…”

Section: Introductionmentioning

confidence: 99%

Controlling the Impact of Helicobacter pylori-Related Hyperhomocysteinemia on Neurodegeneration

et al. 2023

View full text Add to dashboard Cite

Helicobacter pylori infection consists a high global burden affecting more than 50% of the world’s population. It is implicated, beyond substantiated local gastric pathologies, i.e., peptic ulcers and gastric cancer, in the pathophysiology of several neurodegenerative disorders, mainly by inducing hyperhomocysteinemia-related brain cortical thinning (BCT). BCT has been advocated as a possible biomarker associated with neurodegenerative central nervous system disorders such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and/or glaucoma, termed as “ocular Alzheimer’s disease”. According to the infection hypothesis in relation to neurodegeneration, Helicobacter pylori as non-commensal gut microbiome has been advocated as trigger and/or mediator of neurodegenerative diseases, such as the development of Alzheimer’s disease. Among others, Helicobacter pylori-related inflammatory mediators, defensins, autophagy, vitamin D, dietary factors, role of probiotics, and some pathogenetic considerations including relevant involved genes are discussed within this opinion article. In conclusion, by controlling the impact of Helicobacter pylori-related hyperhomocysteinemia on neurodegenerative disorders might offer benefits, and additional research is warranted to clarify this crucial topic currently representing a major worldwide burden.

show abstract

“…Multiple sources indicate that mitochondrial dysfunction plays a crucial role in neurodegenerative processes in Parkinson's [10] and Alzheimer's disease (AD) [11]. Mitochondrial dysfunction can affect the communication organelles of a cell.…”

Section: Introductionmentioning

confidence: 99%

Screening of Crucial Cytosolicproteins Interconnecting the Endoplasmic Reticulum and Mitochondria in Parkinson’s Disease and the Impact of Anti-Parkinson Drugs in the Preservation of Organelle Connectivity

Anirudhan,

Mahema,

Ahmad

et al. 2023

Brain Sciences

View full text Add to dashboard Cite

Mitochondrial dysfunction is well-established in Parkinson’s disease (PD); however, its dysfunctions associating with cell organelle connectivity remain unknown. We aimed to establish the crucial cytosolic protein involved in organelle connectivity between mitochondria and the endopalmic reticulum (ER) through a computational approach by constructing an organelle protein network to extract functional clusters presenting the crucial PD protein connecting organelles. Then, we assessed the influence of anti-parkinsonism drugs (n = 35) on the crucial protein through molecular docking and molecular dynamic simulation and further validated its gene expression in PD participants under, istradefylline (n = 25) and amantadine (n = 25) treatment. Based on our investigation, D-aspartate oxidase (DDO )protein was found to be the critical that connects both mitochondria and the ER. Further, molecular docking showed that istradefylline has a high affinity (−9.073 kcal/mol) against DDO protein, which may disrupt mitochondrial-ER connectivity. While amantadine (−4.53 kcal/mol) shows negligible effects against DDO that contribute to conformational changes in drug binding, Successively, DDO gene expression was downregulated in istradefylline-treated PD participants, which elucidated the likelihood of an istradefylline off-target mechanism. Overall, our findings illuminate the off-target effects of anti-parkinsonism medications on DDO protein, enabling the recommendation of off-target-free PD treatments.

show abstract

Common Mechanisms Underlying α-Synuclein-Induced Mitochondrial Dysfunction in Parkinson’s Disease

Cited by 22 publications

References 225 publications

Cell-Penetrating Peptides: Promising Therapeutics and Drug-Delivery Systems for Neurodegenerative Diseases

Cell-Penetrating Peptides: Promising Therapeutics and Drug-Delivery Systems for Neurodegenerative Diseases

Controlling the Impact of Helicobacter pylori-Related Hyperhomocysteinemia on Neurodegeneration

Screening of Crucial Cytosolicproteins Interconnecting the Endoplasmic Reticulum and Mitochondria in Parkinson’s Disease and the Impact of Anti-Parkinson Drugs in the Preservation of Organelle Connectivity

Contact Info

Product

Resources

About