A Molecular Web: Endoplasmic Reticulum Stress, Inflammation, and Oxidative Stress

Frontiers in Cellular Neuroscience, Journal Year: 2014, Volume and Issue: 8

Published: July 29, 2014

Execution of fundamental cellular functions demands regulated protein folding homeostasis. Endoplasmic reticulum (ER) is an active organelle existing to implement this function by and modifying secretory membrane proteins. Loss homeostasis central various diseases budding evidences suggest ER stress as being a major contributor in the development or pathology diseased state besides other stresses. The trigger for may be diverse but, inflammation and/or basic mechanisms increasing severity complicating condition disease. Chronic activation unfolded response (UPR) through endogenous exogenous insults result impaired calcium redox homeostasis, oxidative via overload thereby also influencing vital mitochondrial functions. Calcium released from augments production Reactive Oxygen Species (ROS). Toxic accumulation ROS within mitochondria disturb Sustained known potentially elicit inflammatory responses UPR pathways. Additionally, generated dysfunction could accelerate malfunction. Dysfunctional pathways has been associated with wide range including several neurodegenerative diseases, stroke, metabolic disorders, cancer, disease, diabetes mellitus, cardiovascular disease others. In review we have discussed signaling pathways, networking between induced events which further induce exacerbate stress.

Language: Английский

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Metals, oxidative stress and neurodegeneration: A focus on iron, manganese and mercury

Neurochemistry International, Journal Year: 2012, Volume and Issue: 62(5), P. 575 - 594

Published: Dec. 22, 2012

Language: Английский

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Mitochondrial Dysfunction and Biogenesis in Neurodegenerative diseases: Pathogenesis and Treatment

CNS Neuroscience & Therapeutics, Journal Year: 2016, Volume and Issue: 23(1), P. 5 - 22

Published: Nov. 22, 2016

Summary Neurodegenerative diseases are a heterogeneous group of disorders that incurable and characterized by the progressive degeneration function structure central nervous system ( CNS ) for reasons not yet understood. Neurodegeneration is umbrella term death nerve cells loss brain tissue. Because their high energy requirements, neurons especially vulnerable to injury from dysfunctional mitochondria. Widespread damage mitochondria causes die because they can no longer produce enough energy. Several lines pathological physiological evidence reveal impaired mitochondrial dynamics play crucial roles in aging pathogenesis neurodegenerative diseases. As major intracellular organelles regulate both cell survival death, highly considered as potential target pharmacological‐based therapies. The purpose this review was present current status our knowledge understanding involvement dysfunction including Alzheimer's disease AD ), Parkinson's PD Huntington's HD amyotrophic lateral sclerosis ALS importance biogenesis novel therapeutic treatment. Likewise, we highlight concise overview key electron transport chain ETC. complexes well regulators regarding those

Language: Английский

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Identification of Altered Metabolic Pathways in Plasma and CSF in Mild Cognitive Impairment and Alzheimer’s Disease Using Metabolomics

PLoS ONE, Journal Year: 2013, Volume and Issue: 8(5), P. e63644 - e63644

Published: May 20, 2013

Alzheimer's Disease (AD) currently affects more than 5 million Americans, with numbers expected to grow dramatically as the population ages. The pathophysiological changes in AD patients begin decades before onset of dementia, highlighting urgent need for development early diagnostic methods. Compelling data demonstrate that increased levels amyloid-beta compromise multiple cellular pathways; thus, investigation various networks is essential advance our understanding disease mechanisms and identify novel therapeutic targets. We applied a liquid chromatography/mass spectrometry-based non-targeted metabolomics approach determine global metabolic plasma cerebrospinal fluid (CSF) from same individuals different severity. Metabolic profiling detected total significantly altered 342 351 CSF metabolites, which 22% were identified. Based on >150 we found 23 canonical pathways 20 mild cognitive impairment (MCI) vs. cognitively normal (CN) false discovery rate <0.05. number affected severity both fluids. Lysine metabolism Krebs cycle MCI CN. Cholesterol sphingolipids transport was Other 30 disturbed included energy metabolism, cycle, mitochondrial function, neurotransmitter amino acid lipid biosynthesis. Pathways discriminated between all groups polyamine, lysine, tryptophan aminoacyl-tRNA biosynthesis; involved cortisone prostaglandin 2 biosynthesis metabolism. Our suggest could shared progression CN AD.

Language: Английский

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There's Something Wrong with my MAM; the ER–Mitochondria Axis and Neurodegenerative Diseases

Trends in Neurosciences, Journal Year: 2016, Volume and Issue: 39(3), P. 146 - 157

Published: Feb. 16, 2016

TrendsMitochondria and the ER form close physical contacts.ER–mitochondria contacts regulate functions damaged in neurodegenerative diseases.ER–mitochondria are diseases.AbstractAlzheimer's disease (AD), Parkinson's (PD), amyotrophic lateral sclerosis with associated frontotemporal dementia (ALS/FTD) major diseases for which there no cures. All characterised by damage to several seemingly disparate cellular processes. The broad nature of this makes understanding pathogenic mechanisms devising new treatments difficult. Can different be linked together a common pathway function should targeted therapy? Many regulated communications that mitochondria make specialised region endoplasmic reticulum (ER; mitochondria-associated membranes or 'MAM'). Moreover, recent studies have shown disturbances ER–mitochondria occur diseases. Here, we review these findings.

Language: Английский

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Phase Separation and Neurodegenerative Diseases: A Disturbance in the Force

Developmental Cell, Journal Year: 2020, Volume and Issue: 55(1), P. 45 - 68

Published: Oct. 1, 2020

Language: Английский

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Estrogen Effects on Cognitive and Synaptic Health Over the Lifecourse

Physiological Reviews, Journal Year: 2015, Volume and Issue: 95(3), P. 785 - 807

Published: June 25, 2015

Estrogen facilitates higher cognitive functions by exerting effects on brain regions such as the prefrontal cortex and hippocampus. induces spinogenesis synaptogenesis in these two also initiates a complex set of signal transduction pathways via estrogen receptors (ERs). Along with classical genomic mediated activation ER α β, there are membrane-bound α, G protein-coupled receptor 1 (GPER1) that can mediate rapid nongenomic effects. All key ERs present throughout body synapses hippocampus cortex. This review summarizes actions from standpoint their synapse structure function, noting synergistic role progesterone. We first begin subtypes how abundance distributions altered aging loss (e.g., ovariectomy or menopause) rodent, monkey, human brain. As is much evidence induced menopause exacerbate functions, we then clinical trials hormone replacement therapies effectiveness symptoms experienced women. Finally, summarize studies carried out nonhuman primate models age- menopause-related decline highly relevant for developing effective interventions menopausal Together, highlight new understanding affects synaptic health go well beyond its reproduction.

Language: Английский

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Mitochondrial Dysfunction in Parkinson’s Disease

Experimental Neurobiology, Journal Year: 2015, Volume and Issue: 24(2), P. 103 - 116

Published: June 23, 2015

Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons substantia nigra pars compacta (SNc) with motor and nonmotor symptoms. Defective mitochondrial function increased oxidative stress (OS) have been demonstrated as having an important role in PD pathogenesis, although underlying mechanism not clear. The etiopathogenesis sporadic complex variable contributions environmental factors genetic susceptibility. Both these influence various aspects, including their life cycle, bioenergetic capacity, quality control, dynamic changes morphology connectivity (fusion, fission), subcellular distribution (transport), regulation cell death pathways. Mitochondrial dysfunction has mainly reported non-dopaminergic cells tissue samples from human patients well transgenic mouse fruit fly models PD. Thus, mitochondria represent a highly promising target for development biomarkers. However, limited amount prevented investigation detailed study. For first time, we established telomerase reverse transcriptase (hTERT)-immortalized wild type, idiopathic Parkin deficient mesenchymal stromal (MSCs) isolated adipose tissues patients, which could be used good cellular model to evaluate better understanding pathology early diagnostic markers effective therapy targets In this review, examine evidence roles OS neuronal that leads discuss how knowledge further improve treatment

Language: Английский

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NAD ⁺ supplementation reduces neuroinflammation and cell senescence in a transgenic mouse model of Alzheimer’s disease via cGAS–STING

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(37)

Published: Sept. 8, 2021

Significance Impaired neuronal bioenergetics and neuroinflammation are thought to play key roles in the progression of Alzheimer's disease (AD), but their interplay is not clear. AD mouse brains showed lower nicotinamide adenine dinucleotide (NAD + ) levels alterations inflammation. Treatment mice with NR reduced neuroinflammation, attenuated DNA damage, prevented cellular senescence. We present evidence that beneficial effects riboside (NR) are, part, through a cyclic GMP-AMP synthase (cGAS)–stimulator interferon genes (STING)-dependent pathway. damage was increased by NR. Both cGAS–STING NAD pathways potential therapeutic targets for AD.

Language: Английский

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Phosphatidylethanolamine Deficiency in Mammalian Mitochondria Impairs Oxidative Phosphorylation and Alters Mitochondrial Morphology

Journal of Biological Chemistry, Journal Year: 2012, Volume and Issue: 288(6), P. 4158 - 4173

Published: Dec. 19, 2012

Language: Английский

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