Novel Insights into the Role of Mitochondria in Neuropsychiatric and Neurodegenerative Disorders

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cells of the Nervous System".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 2801

Special Issue Editor


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Guest Editor
1. Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-531 Coimbra, Portugal
2. Faculty of Medicine, University of Coimbra, 3004-531 Coimbra, Portugal
Interests: neurons; mitochondria; calcium homeostasis; cell death; neurodegenerative disorders

Special Issue Information

Dear Colleagues,

Defects in mitochondrial function, dynamics and/or degradation have been largely described in defining the pathological mechanisms of several neurodegenerative disorders. Other evidence reports pre-symptomatic and early stage changes in different mitochondrial pathways, including redox modulation, mitochondrial quality control or the crosstalk with other organelles, as well as the transport of mitochondrial components between brain cells, revealing additional cellular mechanisms through which these “neuro-essential” organelles may be affected. Furthermore, many of these aspects have also been suggested to occur in different (neuro) psychiatric diseases, while various neurodegenerative diseases encompass early psychiatric symptoms. Neurodegenerative disorders include diverse clinical and pathological pathologies, characterized by progressive symptomatology, affecting selective brain areas and leading to cognitive decline, as well as the loss of memory and daily life functions. On the other hand, neuropsychiatric disorders encompass different mental diseases for which a fundamental neurobiological understanding has been suggested to explain behavioral development. Unfortunately, there is still no cure or neuroprotective treatments for these debilitating neuropsychiatric and neurodegenerative diseases, which supports the need for urgently identifying early diagnosis indicators and novel therapeutic targets and strategies for preventing or delaying the progression of these brain diseases.

This issue aims to cover the different aspects through which mitochondria may play a relevant role in both neuropsychiatric and neurodegenerative disorders.

Dr. Ana Cristina Rego
Guest Editor

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Keywords

  • mitochondria
  • redox changes
  • autophagy
  • therapies
  • brain
  • exossomes
  • intercellular transport
  • mitophagy
  • mitochondrial quality control
  • mitochondria-associated membrane
  • psychiatric diseases
  • synapses
  • mitochondrial transport
  • neurodegeneration
  • synaptic dysfunction

Published Papers (2 papers)

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Research

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18 pages, 2091 KiB  
Article
Mitochondrial Dysfunction and Decreased Cytochrome c in Cell and Animal Models of Machado–Joseph Disease
by Filipa Almeida, Ildete L. Ferreira, Luana Naia, Daniela Marinho, Ana Catarina Vilaça-Ferreira, Marta D. Costa, Sara Duarte-Silva, Patrícia Maciel and A. Cristina Rego
Cells 2023, 12(19), 2397; https://doi.org/10.3390/cells12192397 - 03 Oct 2023
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Abstract
Mitochondrial dysfunction has been described in many neurodegenerative disorders; however, there is less information regarding mitochondrial deficits in Machado–Joseph disease (MJD), a polyglutamine (polyQ) disorder caused by CAG repeat expansion in the ATXN3 gene. In the present study, we characterized the changes in [...] Read more.
Mitochondrial dysfunction has been described in many neurodegenerative disorders; however, there is less information regarding mitochondrial deficits in Machado–Joseph disease (MJD), a polyglutamine (polyQ) disorder caused by CAG repeat expansion in the ATXN3 gene. In the present study, we characterized the changes in mitochondrial function and biogenesis markers in two MJD models, CMVMJD135 (MJD135) transgenic mice at a fully established phenotype stage and tetracycline-regulated PC6-3 Q108 cell line expressing mutant ataxin-3 (mATXN3). We detected mATXN3 in the mitochondrial fractions of PC6-3 Q108 cells, suggesting the interaction of expanded ATXN3 with the organelle. Interestingly, in both the cerebella of the MJD135 mouse model and in PC6-3 Q108 cells, we found decreased mitochondrial respiration, ATP production and mitochondrial membrane potential, strongly suggesting mitochondrial dysfunction in MJD. Also, in PC6-3 Q108 cells, an additional enhanced glycolytic flux was observed. Supporting the functional deficits observed in MJD mitochondria, MJD135 mouse cerebellum and PC6-3 Q108 cells showed reduced cytochrome c mRNA and protein levels. Overall, our findings show compromised mitochondrial function associated with decreased cytochrome c levels in both cell and animal models of MJD. Full article
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Review

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17 pages, 1537 KiB  
Review
Mitochondrial Targeting against Alzheimer’s Disease: Lessons from Hibernation
by Christina F. de Veij Mestdagh, August B. Smit, Robert H. Henning and Ronald E. van Kesteren
Cells 2024, 13(1), 12; https://doi.org/10.3390/cells13010012 - 20 Dec 2023
Cited by 1 | Viewed by 1317
Abstract
Alzheimer’s disease (AD) is the most common cause of dementia worldwide and yet remains without effective therapy. Amongst the many proposed causes of AD, the mitochondrial cascade hypothesis is gaining attention. Accumulating evidence shows that mitochondrial dysfunction is a driving force behind synaptic [...] Read more.
Alzheimer’s disease (AD) is the most common cause of dementia worldwide and yet remains without effective therapy. Amongst the many proposed causes of AD, the mitochondrial cascade hypothesis is gaining attention. Accumulating evidence shows that mitochondrial dysfunction is a driving force behind synaptic dysfunction and cognitive decline in AD patients. However, therapies targeting the mitochondria in AD have proven unsuccessful so far, and out-of-the-box options, such as hibernation-derived mitochondrial mechanisms, may provide valuable new insights. Hibernators uniquely and rapidly alternate between suppression and re-activation of the mitochondria while maintaining a sufficient energy supply and without acquiring ROS damage. Here, we briefly give an overview of mitochondrial dysfunction in AD, how it affects synaptic function, and why mitochondrial targeting in AD has remained unsuccessful so far. We then discuss mitochondria in hibernation and daily torpor in mice, covering current advancements in hibernation-derived mitochondrial targeting strategies. We conclude with new ideas on how hibernation-derived dual mitochondrial targeting of both the ATP and ROS pathways may boost mitochondrial health and induce local synaptic protein translation to increase synaptic function and plasticity. Further exploration of these mechanisms may provide more effective treatment options for AD in the future. Full article
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