The Impact of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis

Zhao, Jiantao; Wang, Xuemei; Huo, Zijun; Chen, Yanchun; Liu, Jinmeng; Zhao, Zhenhan; Meng, Fandi; Su, Qi; Bao, Weiwei; Zhang, Lingyun; Wen, Shuangchun; Wang, Xin; Liu, Huancai; Zhou, Shuanhu

doi:10.3390/cells11132049

Cited by 45 publications

(37 citation statements)

References 147 publications

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“…Amyloid lateral sclerosis (ALS) is a rare, fatal, progressive neurodegenerative disorder for which there is increasing evidence of mitochondrial dysfunction [ 79 ]. Both mitochondrial dysfunction and the degeneration of motor neurons have been associated with oxidative stress that could lead to pathological mitochondrial dysfunction.…”

Section: Reviewmentioning

confidence: 99%

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The Sigma Enigma: A Narrative Review of Sigma Receptors

Pergolizzi¹,

Varrassi²,

Coleman³

et al. 2023

Cureus

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The sigma-1 and sigma-2 receptors were first discovered in the 1960s and were thought to be a form of opioid receptors initially. Over time, more was gradually learned about these receptors, which are actually protein chaperones, and many of their unique or unusual properties can contribute to a range of important new therapeutic applications. These sigma receptors translocate in the body and regulate calcium homeostasis and mitochondrial bioenergetics and they also have neuroprotective effects. The ligands to which these sigma receptors respond are several and dissimilar, including neurosteroids, neuroleptics, and cocaine. There is controversy as to their endogenous ligands. Sigma receptors are also involved in the complex processes of cholesterol homeostasis and protein folding. While previous work on this topic has been limited, research has been conducted in multiple disease states, such as addiction, aging. Alzheimer's disease, cancer, psychiatric disorders, pain and neuropathic pain, Parkinson's disease, and others. There is currently increasing interest in sigma-1 and sigma-2 receptors as they provide potential therapeutic targets for many disease indications.

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Section: Reviewmentioning

confidence: 99%

“…Oxidative stress can cause abnormal aggregation of proteins as well as mutations in mitochondrial DNA. The role of sigma-1 receptors in ALS may be its ability to modulate the calcium balance and reduce oxidative stress [ 79 ].…”

Section: Reviewmentioning

confidence: 99%

The Sigma Enigma: A Narrative Review of Sigma Receptors

Pergolizzi¹,

Varrassi²,

Coleman³

et al. 2023

Cureus

View full text Add to dashboard Cite

show abstract

“…Idiopathic ALS [40,41] Progression of lower motor neuron signs (including EMG features in clinically unaffected muscles) and upper motor neuron signs, muscle atrophy, paralysis, frontotemporal dementia with absence of sensory signs. EMG is characterized by fasciculations in one or more regions, neurogenic changes, normal motor and sensory nerve conduction and absence of conduction blocks.…”

Section: Spinal Cord Compression By the Posterior Dural Sac During Ne...mentioning

confidence: 99%

Amyotrophic Lateral Sclerosis Mimic Syndrome in a 24-Year-Old Man with Chiari 1 Malformation and Syringomyelia: A Clinical Case

Al-Zamil

Shnayder

Davydova³

et al. 2023

JCM

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Chiari 1 Malformation (CM1) is classically defined as a caudal displacement of the cerebellar tonsils through the foramen magnum into the spinal cord. Modern imaging techniques and experimental studies disclose a different etiology for the development of CM1, but the main etiology factor is a structural defect in the skull as a deformity or partial reduction, which push down the lower part of the brain and cause the cerebellum to compress into the spinal canal. CM1 is classified as a rare disease. CM1 can present with a wide variety of symptoms, also non-specific, with consequent controversies on diagnosis and surgical decision-making, particularly in asymptomatic or minimally symptomatic. Other disorders, such as syringomyelia (Syr), hydrocephalus, and craniocervical instability can be associated at the time of the diagnosis or appear secondarily. Therefore, CM1-related Syr is defined as a single or multiple fluid-filled cavities within the spinal cord and/or the bulb. A rare CM1-related disorder is syndrome of lateral amyotrophic sclerosis (ALS mimic syndrome). We present a unique clinical case of ALS mimic syndrome in a young man with CM1 and a huge singular syringomyelic cyst with a length from segment C2 to Th12. At the same time, the clinical picture showed upper hypotonic-atrophic paraparesis in the absence of motor disorders in the lower extremities. Interestingly, this patient did not have a disorder of superficial and deep types of sensitivity. This made it difficult to diagnose CM1. For a long time, the patient’s symptoms were regarded as a manifestation of ALS, as an independent neurological disease, and not as a related disorder of CM1. Surgical treatment for CM1 was not effective, but it allowed to stabilize the course of CM1-related ALS mimic syndrome over the next two years.

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“…Additionally, in SOD1 −/− axons, mitochondria densities decreased and might contribute to distal motor axons deficits due to their great demand for energy inputs. Immature SOD1 and CCS (copper chaperone for superoxide dismutase), which also plays a role in SOD1 maturation by inserting Cu, are imported into the mitochondrial intermembrane space by the translocase of the outer mitochondrial membrane, where they are both trapped by metal insertion and disulfide bond formation mediated by MIA40/ERV1’s disulfide relay system [ 235 , 236 ]. Upon the sudden increase in mitochondrial oxidative stress, CCS-dependent SOD1 maturation within IMS traps SOD1 within the compartment to mitigate acute oxidative insult, and this augments SOD2-mediated superoxide clearance within the mitochondrial matrix [ 235 , 236 ].…”

Section: Redox Ptms In Amyotrophic Lateral Sclerosismentioning

confidence: 99%

S-Glutathionylation and S-Nitrosylation in Mitochondria: Focus on Homeostasis and Neurodegenerative Diseases

Vrettou

Wirth

2022

IJMS

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Redox post-translational modifications are derived from fluctuations in the redox potential and modulate protein function, localization, activity and structure. Amongst the oxidative reversible modifications, the S-glutathionylation of proteins was the first to be characterized as a post-translational modification, which primarily protects proteins from irreversible oxidation. However, a growing body of evidence suggests that S-glutathionylation plays a key role in core cell processes, particularly in mitochondria, which are the main source of reactive oxygen species. S-nitrosylation, another post-translational modification, was identified >150 years ago, but it was re-introduced as a prototype cell-signaling mechanism only recently, one that tightly regulates core processes within the cell’s sub-compartments, especially in mitochondria. S-glutathionylation and S-nitrosylation are modulated by fluctuations in reactive oxygen and nitrogen species and, in turn, orchestrate mitochondrial bioenergetics machinery, morphology, nutrients metabolism and apoptosis. In many neurodegenerative disorders, mitochondria dysfunction and oxidative/nitrosative stresses trigger or exacerbate their pathologies. Despite the substantial amount of research for most of these disorders, there are no successful treatments, while antioxidant supplementation failed in the majority of clinical trials. Herein, we discuss how S-glutathionylation and S-nitrosylation interfere in mitochondrial homeostasis and how the deregulation of these modifications is associated with Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis and Friedreich’s ataxia.

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The Impact of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis

Cited by 45 publications

References 147 publications

The Sigma Enigma: A Narrative Review of Sigma Receptors

The Sigma Enigma: A Narrative Review of Sigma Receptors

Amyotrophic Lateral Sclerosis Mimic Syndrome in a 24-Year-Old Man with Chiari 1 Malformation and Syringomyelia: A Clinical Case

S-Glutathionylation and S-Nitrosylation in Mitochondria: Focus on Homeostasis and Neurodegenerative Diseases

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