Mitochondrial Biology and Neurological Diseases

Arun, Siddharth; Liu, Lei; Dönmez, Gizem

doi:10.2174/1570159x13666150703154541

Cited by 103 publications

(64 citation statements)

References 99 publications

(127 reference statements)

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“…These diseases share the property that mitochondria (MT) do not keep up with the energy demands of the cell (Arun et al, 2016). However, AD, PD, and HD display region-specific cell death (Carvalho et al, 2015), and even within those regions, only select cell types are targeted (Reiner et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

Metabolic Reprogramming in Astrocytes Distinguishes Region-Specific Neuronal Susceptibility in Huntington Mice

et al. 2019

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SUMMARY The basis for region-specific neuronal toxicity in Huntington disease is unknown. Here, we show that region-specific neuronal vulnerability is a substrate-driven response in astrocytes. Glucose is low in HdhQ(150/150) animals, and astrocytes in each brain region adapt by metabolically reprogramming their mitochondria to use endogenous, non-glycolytic metabolites as an alternative fuel. Each region is characterized by distinct metabolic pools, and astrocytes adapt accordingly. The vulnerable striatum is enriched in fatty acids, and mitochondria reprogram by oxidizing them as an energy source but at the cost of escalating reactive oxygen species (ROS)-induced damage. The cerebellum is replete with amino acids, which are precursors for glucose regeneration through the pentose phosphate shunt or gluconeogenesis pathways. ROS is not elevated, and this region sustains little damage. While mhtt expression imposes disease stress throughout the brain, sensitivity or resistance arises from an adaptive stress response, which is inherently region specific. Metabolic reprogramming may have relevance to other diseases.

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Section: Introductionmentioning

confidence: 99%

Metabolic Reprogramming in Astrocytes Distinguishes Region-Specific Neuronal Susceptibility in Huntington Mice

et al. 2019

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“…Alzheimer’s (AD), Parkinson’s (PD), and Huntington’s disease (HD) share the property that mitochondria (MT) do not keep up with the energy demands of the cell (Arun et al, 2016; Carvalho et al, 2015; Chaturvedi and Flint Beal, 2013; Lane et al, 2015). However, AD, PD, and HD display region-specific cell death (Chaturvedi and Flint Beal, 2013; Grimm et al, 2016; Gu et al, 1996; Requejo-Aguilar and Bolanos, 2016) and even within those regions, only select cell types are targeted (Halliday et al, 1998; Reiner et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

The chicken or the egg: mitochondrial dysfunction as a cause or consequence of toxicity in Huntington’s disease

Polyzos

McMurray

2017

Mechanisms of Ageing and Development

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Mitochondrial dysfunction and ensuing oxidative damage is typically thought to be a primary cause of Huntington’s disease, Alzheimer’s disease and Parkinson disease. There is little doubt that mitochondria (MT) become defective as neurons die, yet whether MT defects are the primary cause or a detrimental consequence of toxicity remains unanswered. Oxygen consumption rate (OCR) and glycolysis provide sensitive and informative measures of the functional status MT and the cells metabolic regulation, yet these measures differ depending on the sample source; species, tissue type, age at measurement, and whether MT are measured in purified form or in a cell. The effects of these various parameters are difficult to quantify and not fully understood, but clearly have an impact on interpreting the bioenergetics of MT or their failure in disease states. A major goal of the review is to discuss issues and coalesce detailed information into a reference table to help in assessing mitochondrial dysfunction as a cause or consequence of Huntington’s disease.

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“…Peptoids have also been used as antagonists for apoptotic protease-activating factor-1 (Apaf-1) to render the apoptosome complex inactive 40,41 . Such antagonism impairs mitochondrial-mediated apoptosis, which is associated with many neurodegenerative diseases 42 . Introducing conformational constraint 43 and conjugation of the peptoid to cell penetrating peptides 44 or a polymeric carrier 45 enhance the effectiveness of these peptoids.…”

Section: Peptoids As Neuroprotective Agentsmentioning

confidence: 99%

Peptoids: Emerging Therapeutics for Neurodegeneration

Moss¹

2017

J Neurol Neuromedicine

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In recent decades, the increasing prevalence of age-associated neurodegenerative diseases has underscored the need for targeted therapeutic strategies and novel diagnostics. Peptide-based neurotherapeutics offer high specificity and tolerability but are limited by proteolytic degradation in vivo. Peptoids, or N-substituted glycines, are versatile peptidomimetics that evade proteolytic degradation yet maintain many qualities that render peptides attractive neurotherapeutic candidates. These molecules may be engineered to their application through modifications that enhance structural stability and reactivity and can withstand various physiological stressors to retain their intended function within anomalous microenvironments.Peptoids generally demonstrate greater cellular permeability than their corresponding peptides, are less immunogenic, and can be administered intranasally, all properties that enhance their potential as neurotherapeutics. Peptoids have primarily been explored as aggregation inhibitors to prevent the deleterious protein plaque deposition associated with several neurodegenerative disorders. However, novel research has uncovered the potential of peptoids toward additional neurotherapeutic applications. Peptoids can modulate cell signaling pathways involved in axonal function and current modulation and can block cell signaling events associated with apoptosis. In addition, these peptidomimetics are able to function as anti-inflammatory agents via multiple mechanisms. Moreover, the versatility and low cost of peptoids render them ideal instruments in biomarker detection, discovery, and imaging. This mini-review explores these diverse applications of peptoids within the context of neurodegenerative disease.

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Mitochondrial Biology and Neurological Diseases

Cited by 103 publications

References 99 publications

Metabolic Reprogramming in Astrocytes Distinguishes Region-Specific Neuronal Susceptibility in Huntington Mice

Metabolic Reprogramming in Astrocytes Distinguishes Region-Specific Neuronal Susceptibility in Huntington Mice

The chicken or the egg: mitochondrial dysfunction as a cause or consequence of toxicity in Huntington’s disease

Peptoids: Emerging Therapeutics for Neurodegeneration

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