Mitochondrial Complex I Inhibition in Dopaminergic Neurons Causes Altered Protein Profile and Protein Oxidation: Implications for Parkinson’s disease

Chithra, Yogeshachar; Dey, Gourav; Ghose, Vivek; Chandramohan, Vivek; Gowthami, Niya; Vasudev, Vivek; Bharath, M. M. Srinivas

doi:10.1007/s11064-023-03907-x

Cited by 4 publications

(1 citation statement)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These interactions create a local electrostatic environment produced by the charge differentials of different residues in these subunits. This electrostatic environment permits fine-tuning of redox active residues, which in turn induces modification of other neighboring redox active residues [ 166 , 304 , 305 ]. Also, charged modifications of residues produce conformational transitions of the individual subunits that is propagated to other subunit leading to change in catalytic activity of the complex I [ 70 , 77 , 306 ].…”

Section: Ndufs2 Residues Mediate Acute Hypoxia Behavioral Responsementioning

confidence: 99%

Mitochondrial complex I ROS production and redox signaling in hypoxia

Okoye,

Koren,

Wojtovich

2023

Redox Biology

View full text Add to dashboard Cite

Section: Ndufs2 Residues Mediate Acute Hypoxia Behavioral Responsementioning

confidence: 99%

Mitochondrial complex I ROS production and redox signaling in hypoxia

Okoye,

Koren,

Wojtovich

2023

Redox Biology

View full text Add to dashboard Cite

Bacopa monnieri extract (CDRI-08) recovers recognition memory impairment by upregulation of GluR2 AMPA receptor subunit expression and reduced methylation of its cognate promoter in the hippocampus of rotenone-induced Parkinson’s disease mouse model

Chandra,

Prasad

2023

Preprint

View full text Add to dashboard Cite

Parkinson's disease (PD), an age-dependent neurodegenerative movement disorder, is attributed to the lossof dopaminergic neurons in the striatal SNPc, abnormal α-Synuclein accumulation that leads to complex movement disorders, cognitive dysfunction, and dementia in later stage, however, its precise molecular underpinning is not well known. In the proposed study, we aim to explore the effects of PD on the expression of the synaptic plasticity associated with AMPA receptor subunit GluR2, its epigenetic regulation, and investigate the possible therapeutic role of a well-characterized extract of an ancient Indian medicinal plantBacopa monniericalled CDRI-08 on the PD and memory impairment in rotenone-PD mouse model as presently there is no successful treatment available for curing the PD-induced pathologies. Our immunoblotting and qPCR data showed a significant upregulation of the GluR2 expression in the hippocampus of rotenone-treated mice as compared to the vehicle control group. Our MeDIP-qPCR data revealed that the increased GluR2 expression was significantly correlated with a decline in its promoter CpG methylation in the hippocampus of rotenone-treated mice. CDRI-08 treatment to the rotenone-treated mice significantly lowered the PD pathologies, and GluR2 expression with a subsequent increase in the GluR2 promoter methylation towards the control values in the hippocampus. The current study suggests one of the precise molecular events underlying PD, its effects on memory impairment, and the neurotherapeutic potential of Bacopa monnieri extract, CDRI-08, which might be useful for the treatment of PD-induced movement and cognitive impairments.

show abstract

A mouse model of sporadic Alzheimer’s disease with elements of major depression

Bobkova,

Chuvakova,

Kovalev

et al. 2024

Preprint

View full text Add to dashboard Cite

Animals after bulbectomy are often used as a model of major depression or sporadicAlzheimer’s disease and, hence, the status of this model is still disputable. To elucidate the nature of alterations in the expression of the genome after the operation we analyzed transcriptomes (RNA-seq data) of the cortex, hippocampus, and cerebellum of olfactory bulbectomized (OBX) mice. Analysis of the functional significance of genes in the brain of OBX mice indicates that the balance of the GABA/glutamatergic systems is disturbed with hyperactivation of the latter in the hippocampus leading to the development of excitotoxicity and induction of apoptosis on the background of severe mitochondrial dysfunction and astrogliosis. On top of this, the synthesis of neurotrophic factors decreases leading to the disruption of the cytoskeleton of neurons, an increase in the level of intracellular calcium, and activation of tau protein hyperphosphorylation and beta-amyloid depositions. Moreover, the acetylcholinergic system is deficient in the background of hyperactivation of acetylcholinesterase. Importantly, the activity of the dopaminergic, endorphin, and opiate systems in OBX mice decreases leading to hormonal dysfunction. Genes responsible for the regulation of circadian rhythms, cell migration, and impaired innate immunity are activated in OBX animals. All this takes place on the background of drastic down-regulation of ribosomal protein genes in the brain. The obtained results indicate that OBX mice represent a model of Alzheimer's disease with elements of major depression. This model can be tentatively attributed to AD subtype B2 in humans.

show abstract

Mitochondrial Complex I Inhibition in Dopaminergic Neurons Causes Altered Protein Profile and Protein Oxidation: Implications for Parkinson’s disease

Cited by 4 publications

References 81 publications

Mitochondrial complex I ROS production and redox signaling in hypoxia

Mitochondrial complex I ROS production and redox signaling in hypoxia

Bacopa monnieri extract (CDRI-08) recovers recognition memory impairment by upregulation of GluR2 AMPA receptor subunit expression and reduced methylation of its cognate promoter in the hippocampus of rotenone-induced Parkinson’s disease mouse model

A mouse model of sporadic Alzheimer’s disease with elements of major depression

Contact Info

Product

Resources

About