scholarly journals Mitochondrial dysfunctions in neurodegenerative diseases: role in disease pathogenesis, strategies for analysis and therapeutic prospects

2022 ◽  
Vol 17 (4) ◽  
pp. 754 ◽  
Author(s):  
Stephana Carelli ◽  
Federica Rey ◽  
Sara Ottolenghi ◽  
GianVincenzo Zuccotti ◽  
Michele Samaja
Keyword(s):  
Neurodegenerative Diseases ◽  
Disease Pathogenesis ◽  
Mitochondrial Dysfunctions

Excitotoxicity as a Target Against Neurodegenerative Processes

2020 ◽  
Vol 26 (12) ◽  
pp. 1251-1262 ◽  
Author(s):  
Octavio Binvignat ◽  
Jordi Olloquequi
Keyword(s):  
Neurodegenerative Diseases ◽  
Effective Treatment ◽  
Molecular Mechanisms ◽  
Prolonged Exposure ◽  
Mitochondrial Dysfunctions ◽  
Beneficial Effects ◽  
Clinical Investigations ◽  
Turn Over ◽  
Excitotoxic Cell Death ◽  
Lateral Sclerosis

: The global burden of neurodegenerative diseases is alarmingly increasing in parallel to the aging of population. Although the molecular mechanisms leading to neurodegeneration are not completely understood, excitotoxicity, defined as the injury and death of neurons due to excessive or prolonged exposure to excitatory amino acids, has been shown to play a pivotal role. The increased release and/or decreased uptake of glutamate results in dysregulation of neuronal calcium homeostasis, leading to oxidative stress, mitochondrial dysfunctions, disturbances in protein turn-over and neuroinflammation. : Despite the anti-excitotoxic drug memantine has shown modest beneficial effects in some patients with dementia, to date, there is no effective treatment capable of halting or curing neurodegenerative diseases such as Alzheimer’s disease, Parkinson disease, Huntington’s disease or amyotrophic lateral sclerosis. This has led to a growing body of research focusing on understanding the mechanisms associated with the excitotoxic insult and on uncovering potential therapeutic strategies targeting these mechanisms. : In the present review, we examine the molecular mechanisms related to excitotoxic cell death. Moreover, we provide a comprehensive and updated state of the art of preclinical and clinical investigations targeting excitotoxic- related mechanisms in order to provide an effective treatment against neurodegeneration.

Delayed luminescence for in vitro study of mitochondrial dysfunctions in neurodegenerative diseases

2019 ◽  
Author(s):  
Rosaria Grasso ◽  
Rosalia Pellitteri ◽  
Francesco Musumeci ◽  
Rosaria V. Rapicavoli ◽  
Giovanni Sposito ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
In Vitro Study ◽  
Vitro Study ◽  
Delayed Luminescence ◽  
Mitochondrial Dysfunctions

scholarly journals Mitochondrial Dysfunctions: A Red Thread across Neurodegenerative Diseases

2020 ◽  
Vol 21 (10) ◽  
pp. 3719 ◽  
Author(s):  
Serena Stanga ◽  
Anna Caretto ◽  
Marina Boido ◽  
Alessandro Vercelli
Keyword(s):  
Neurodegenerative Diseases ◽  
Neuronal Degeneration ◽  
Muscular Atrophy ◽  
Early Event ◽  
Mitochondrial Dysfunctions ◽  
The Core ◽  
Optimal Functioning ◽  
Mitochondrial Functions ◽  
Lateral Sclerosis ◽  
Common Target

Mitochondria play a central role in a plethora of processes related to the maintenance of cellular homeostasis and genomic integrity. They contribute to preserving the optimal functioning of cells and protecting them from potential DNA damage which could result in mutations and disease. However, perturbations of the system due to senescence or environmental factors induce alterations of the physiological balance and lead to the impairment of mitochondrial functions. After the description of the crucial roles of mitochondria for cell survival and activity, the core of this review focuses on the “mitochondrial switch” which occurs at the onset of neuronal degeneration. We dissect the pathways related to mitochondrial dysfunctions which are shared among the most frequent or disabling neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s, Amyotrophic Lateral Sclerosis, and Spinal Muscular Atrophy. Can mitochondrial dysfunctions (affecting their morphology and activities) represent the early event eliciting the shift towards pathological neurobiological processes? Can mitochondria represent a common target against neurodegeneration? We also review here the drugs that target mitochondria in neurodegenerative diseases.

scholarly journals Mitochondrial dysfunctions and neurodegenerative diseases: a mini-review

2021 ◽  
Vol 10 (4) ◽  
pp. 147-149
Author(s):  
Ratan Kumari ◽  
Nikhila Shekhar ◽  
Sakshi Tyagi ◽  
Ajit Kumar Thakur
Keyword(s):  
Reactive Oxygen Species ◽  
Neurodegenerative Diseases ◽  
Mitochondrial Dysfunction ◽  
Neurodegenerative Disorders ◽  
Oxygen Species ◽  
Primary Reason ◽  
Mitochondrial Dysfunctions ◽  
Detailed Understanding ◽  
Age Related ◽  
Different Types

Mitochondrial dysfunction is estimated to be the primary reason involved in different types of neurodegenerative disorders as mitochondria is suggested to be important in the production of reactive oxygen species. Recently, several evidences have emerged out for impaired mitochondrial structures and functions viz. shape, size, fission-fusion, distribution, movement etc. in neurodegenerative diseases especially with Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. Therefore, apart from looking neurodegenerative diseases on the whole, a detailed understanding of the functioning of mitochondria and their role in degeneration would pave new options for the therapy of age-related neurodegenerative diseases.

scholarly journals Mitochondrial Dysfunction: a Notable Contributor to the Progression of Alzheimer’s & Parkinson’s Disease

2021 ◽  
Author(s):  
Abolaji Samson Olagunju ◽  
Abiola Adeyanju Alagbe ◽  
Titilayomi Ayomide Otenaike ◽  
Babatunde Oladayo Fabiyi ◽  
John Oluwafemi Teibo ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Mitochondrial Dysfunction ◽  
Cell Biology ◽  
Focal Point ◽  
Dominant Role ◽  
Early Event ◽  
Parkinsons Disease ◽  
Mitochondrial Dysfunctions ◽  
Mitochondrial Homeostasis ◽  
Mitochondrial Functions

Mitochondrial dysfunctions remained a pivotal mechanism in manifold neurodegenerative diseases. Mitochondrial homeostasis within the cell is an essential aspect of cell biology. Mitochondria which is also known as the power-generating set of the cell, have a dominant role in several processes associated with the genomic integrity and cellular equilibrium maintenance. They are involved in maintaining optimal cells functioning and guidance from possible DNA damage which could lead to mutations and onset of diseases. Conversely, system perturbations which could be due to environmental factors or senescence induce changes in the physiological balance and result in the mitochondrial functions impairment. The focal point of this review focuses on mitochondrial dysfunction as a significant condition in the onset of neuronal disintegration. We explain the pathways associated with the dysfunction of the mitochondria which are common amongst the most recurring neurodegenerative diseases including Alzheimers and Parkinsons disease. Do mitochondrial dysfunctions represent an early event in causing a shift towards neuropathological processes?

scholarly journals Intercellular Spread of Protein Aggregates in Neurodegenerative Disease

2018 ◽  
Vol 34 (1) ◽  
pp. 545-568 ◽  
Author(s):  
Albert A. Davis ◽  
Cheryl E.G. Leyns ◽  
David M. Holtzman
Keyword(s):  
Neurodegenerative Diseases ◽  
Protein Aggregation ◽  
Neurodegenerative Disease ◽  
Extracellular Space ◽  
Protein Aggregates ◽  
Therapeutic Strategies ◽  
Disease Pathogenesis ◽  
Donor Cells ◽  
Intercellular Spread

Most neurodegenerative diseases are characterized by the accumulation of protein aggregates, some of which are toxic to cells. Mounting evidence demonstrates that in several diseases, protein aggregates can pass from neuron to neuron along connected networks, although the role of this spreading phenomenon in disease pathogenesis is not completely understood. Here we briefly review the molecular and histopathological features of protein aggregation in neurodegenerative disease, we summarize the evidence for release of proteins from donor cells into the extracellular space, and we highlight some other mechanisms by which protein aggregates might be transmitted to recipient cells. We also discuss the evidence that supports a role for spreading of protein aggregates in neurodegenerative disease pathogenesis and some limitations of this model. Finally, we consider potential therapeutic strategies to target spreading of protein aggregates in the treatment of neurodegenerative diseases.

scholarly journals Nrf2/ARE Signaling Pathway: Key Mediator in Oxidative Stress and Potential Therapeutic Target in ALS

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Susanne Petri ◽  
Sonja Körner ◽  
Mahmoud Kiaei
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Motor Neurons ◽  
Leucine Zipper ◽  
Antioxidant Response ◽  
Related Factor ◽  
Mitochondrial Dysfunctions ◽  
Promising Target ◽  
Basic Region ◽  
Lateral Sclerosis

Nrf2 (nuclear erythroid 2-related factor 2) is a basic region leucine-zipper transcription factor which binds to the antioxidant response element (ARE) and thereby regulates the expression of a large battery of genes involved in the cellular antioxidant and anti-inflammatory defence as well as mitochondrial protection. As oxidative stress, inflammation and mitochondrial dysfunctions have been identified as important pathomechanisms in amyotrophic lateral sclerosis (ALS), this signaling cascade has gained interest both with respect to ALS pathogenesis and therapy. Nrf2 and Keap1 expressions are reduced in motor neurons in postmortem ALS tissue. Nrf2-activating compounds have shown therapeutic efficacy in the ALS mouse model and other neurodegenerative disease models. Alterations in Nrf2 and Keap1 expression and dysregulation of the Nrf2/ARE signalling program could contribute to the chronic motor neuron degeneration in ALS and other neurodegenerative diseases. Therefore, Nrf2 emerges as a key neuroprotective molecule in neurodegenerative diseases. Our recent studies strongly support that the Nrf2/ARE signalling pathway is an important mediator of neuroprotection and therefore represents a promising target for development of novel therapies against ALS, Parkinson’s disease (PD), Huntington’s disease (HD), and Alzheimer’s disease (AD).

Aging of Brain Related with Mitochondrial Dysfunctions

2020 ◽  
Vol 21 ◽  
Author(s):  
Vipin Dhote ◽  
Prem Samundre ◽  
Aditya Ganeshpurkar ◽  
Aman Upaganlawar
Keyword(s):  
Neurodegenerative Diseases ◽  
Psychiatric Symptoms ◽  
Neuronal Damage ◽  
The Elderly ◽  
Environmental Chemicals ◽  
Aging Brain ◽  
Mitochondrial Dysfunctions ◽  
Mitochondrial Functions ◽  
Key Issues ◽  
The Brain

Abstract:: Advancing age presents a major challenge for the elderly population in terms of quality of life. The risk of cognitive impairment, motor in-coordination, and behavioral inconsistency due to neuronal damage is relatively higher in aging individuals of society. The brain, through its structural and functional integrity, regulates vital physiological events; however, the susceptibility of the brain to aging-related disturbances signal the onset of neurodegenerative diseases. Mitochondrial dysfunctions impair bioenergetic mechanism, synaptic plasticity, and calcium homeostasis in the brain, thus sufficiently implying mitochondria as a prime causal factor in accelerating aging-related neurodegeneration. We reviewed the fundamental functions of mitochondria in a healthy brain and aimed to address the key issues in aging-related diseases by asking: 1) What goes wrong with mitochondria in the aging brain? 2) What are the implications of mitochondrial damage on motor functions and psychiatric symptoms? 3) How environmental chemicals and metabolic morbidities affect mitochondrial functions? Further, we share insight on opportunities and pitfalls in drug discovery approaches targeting mitochondria to slow down the progression of aging and related neurodegenerative diseases.

Mitochondrial dysfunction plays a key role in the development of neurodegenerative diseases in diabetes

2020 ◽  
Vol 318 (5) ◽  
pp. E750-E764 ◽  
Author(s):  
Han Cheng ◽  
Xiaokun Gang ◽  
Yujia Liu ◽  
Gang Wang ◽  
Xue Zhao ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Reactive Oxygen Species Generation ◽  
Hypoglycemic Agents ◽  
Neuroprotective Effects ◽  
Mitochondrial Dysfunctions ◽  
Dipeptidyl Peptidase 4 ◽  
Beneficial Effects ◽  
Glucagon Like Peptide 1

Mitochondria have an essential function in cell survival due to their role in bioenergetics, reactive oxygen species generation, calcium buffering, and other metabolic activities. Mitochondrial dysfunctions are commonly found in neurodegenerative diseases (NDs), and diabetes is a risk factor for NDs. However, the role of mitochondria in diabetic neurodegeneration is still unclear. In the present study, we review the latest evidence on the role of mitochondrial dysfunctions in the development of diabetes-related NDs and the underlying molecular mechanisms. Hypoglycemic agents, especially metformin, have been proven to have neuroprotective effects in the treatment of diabetes, in which mitochondria could act as one of the underlying mechanisms. Other hypoglycemic agents, including thiazolidinediones (TZDs), dipeptidyl peptidase 4 (DPP-4) inhibitors, and glucagon-like peptide 1 (GLP-1) receptor agonists, have gained more attention because of their beneficial effects on NDs, presumably by improving mitochondrial function. Our review highlights the notion that mitochondria could be a promising therapeutic target in the treatment of NDs in patients with diabetes.

scholarly journals Mitochondrial Dysfunctions in Neurodegenerative Diseases: Relevance to Alzheimer’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Jana Hroudová ◽  
Namrata Singh ◽  
Zdeněk Fišar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Electron Transport ◽  
Neurodegenerative Diseases ◽  
Electron Transport Chain ◽  
Nuclear Dna ◽  
Early Stage ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Dysfunctions ◽  
Transport Chain

Mitochondrial dysfunctions are supposed to be responsible for many neurodegenerative diseases dominating in Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD). A growing body of evidence suggests that defects in mitochondrial metabolism and particularly of electron transport chain may play a role in pathogenesis of AD. Structurally and functionally damaged mitochondria do not produce sufficient ATP and are more prominent in producing proapoptotic factors and reactive oxygen species (ROS), and this can be an early stage of several mitochondrial disorders, including neurodegenerative diseases. Mitochondrial dysfunctions may be caused by both mutations in mitochondrial or nuclear DNA that code mitochondrial components and by environmental causes. In the following review, common aspects of mitochondrial impairment concerned about neurodegenerative diseases are summarized including ROS production, impaired mitochondrial dynamics, and apoptosis. Also, damaged function of electron transport chain complexes and interactions between pathological proteins and mitochondria are described for AD particularly and marginally for PD and HD.

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