Mitochondrial dysfunction

…It connects mitochondrial dysfunction, cellular aging, immune activation, inflammation and microbiome interactions with injury in the liver, gut, brain and cardiovascular system and with cancer. Organoids and other experimental platforms support discussion of therapeutic strategies, alongside integrated treatment of alcohol use disorder and end-organ damage. Talks, poster sessions and discussion focus on emerging and unpublished research. Applicants need a science or engineering bachelor’s degree or equivalen

Meagan McManus examines mitochondrial dysfunction as an early driver of brain ageing and neurodegeneration. Reactive oxygen species and other mitochondrial stress signals connect impaired energy metabolism with glial activation. The talk presents preclinical evidence for [18F]ROStrace PET, a redox-sensitive tracer that crosses the blood–brain barrier, as a non-invasive way to detect mitochondrial and immune distress before overt pathology in models relevant to late-onset Alzheimer’s and Parkinson’s diseases. Online via the University of Arizona Zoom meeting. Use the Zoom link published on the

…Brain aging involves mitochondrial dysfunction, dysregulated energy metabolism, altered neuronal activity, and inflammation. Changes in white matter metabolism during aging are poorly understood. In this study, we

The molecular nature of psychiatric disorders such as schizophrenia and major depression is still unclear. Lipids may play an important role in the understanding of these disorders, as they are the most abundant yet poorly studied components of the human brain. In this work, we present a comparative lipidomic map of the human brain affected by schizophrenia or major depressive disorder. The study involved three groups of donors, 7 donors each, which included schizophrenic and depressive donors as well as healthy controls. The lipid composition of 36 brain regions was evaluated by liquid chroma

…years it has been hypothesized that mitochondrial dysfunction and energy metabolism dysregulation may contribute to the pathophysiology of schizophrenia [1]. Therefore, we studied the mRNA expression of the prefrontal cortex (PFC) using the CommonMind data set [2] to find out if there is a significant enrichment of differentially expressed metabolism genes between control group and schizophrenia patients. In additi

Prodromal network hyperexcitability and mitochondrial dysfunction underly the pathogenesis of various forms of dementia. However, the role of hippocampal hyperexcitability and mitochondria in prodromal dementia with Lewy bodies (DLB) is unclear.We conducted multi-electrode array (MEA) recordings to investigate early hippocampal activity in a transgenic mouse model of DLB which harbours an alanine to proline point mutation (A30P) in the alpha synuclein gene (SNCA), causing overexpression. Hippocampal slices from young pre-symptomatic (2-4 months) male A30P (N = 6 slices/4 mice) and wild-type (W

Mitochondrial dysfunctions are common findings in neurodegenerative diseases, particularly in Parkinson's disease(PD), where alpha-synuclein encoded by the SNCA gene has been observed to localize within the organelle as the disease progresses. Despite alpha-synuclein's significance in PD pathology, its specific roles within mitochondria still need to be better understood. In this study, we aimed to explore the impact of overexpression of the SNCA gene, which codes for the alpha-synuclein protein, on the expression of genes encoded by mitochondrial DNA (mtDNA).HEK-293T cells were transfected wi

Transglutaminase 2 (TG2) is a widespread enzyme in the transglutaminase family, which consists of nine multifunctional proteins that evolved from the papain family. TG2 is ubiquitously expressed across various tissues and cell types. Its primary role is catalyzing the formation of a durable isopeptide bond through the Ca2+-dependent covalent linkage between the γ-carboxamide group of peptide-bound glutamine and the ε-amino group of lysine in proteins. This enzymatic process results in a proteolytically-resistant bond. Significantly, TG2 activity is observed to increase in several neurodegenera

A strong link between the SHANK3 gene mutations and autism spectrum disorder (ASD) has been established but its molecular mechanisms remain unknown. Here we hypothesize that a mutation in the Shank3 gene leads to alterations in the global proteome, and consequently, these alterations converge into cellular and behavioral deficits of ASD. To test this hypothesis, we comprehensively mapped the global proteome within the cortex of the Shank3Δ4-22 mice. Our preliminary results revealed a significant increase in one of the ATP synthase subunits (ATP-S) expression levels in the cortex of Shank3Δ4-22

Mitochondrial dysfunction has been detected in the brains of patients with autism spectrum disorders (ASD) with unclear mechanisms. We herein identify that G protein-coupled receptor 50 (GPR50), which harbors two variations in male ASD patients at Δ502-505 and T532A, is required in mitophagy. GPR50, which does not distribute endogenously in the mitochondrion, is recruited to the damaged mitochondrion, where it marks the mitochondrial portion and recruits the assembling autophagosomes, eventually facilitating itself with the mitochondrial fragments to the autophagosomes. The above process is as

Mitochondrial dysfunction has been implicated in psychiatric disorders, yet the specific cellular and molecular mechanisms remain elusive. Previous research has identified a connection between high trait anxiety and low levels of mitofusin 2 (Mfn2), a mitochondrial fusion protein, in the nucleus accumbens (NAc), a brain region crucial for motivation and goal-directed behavior. To assess the implications of Mfn2 in a cell-type specific manner, in this study we selectively manipulated Mfn2 in NAc dopamine receptor 1-expressing medium spiny neurons (D1-MSNs) using a viral vector (AAV1-Dyn-CRE) in

…Mitochondrial lysate isolations were per

…sensitive to oxidative stress (OS) and mitochondrial impairment, conditions that are well known to increase with ageing. Therefore, there is a critical n

Aims: Mitochondrial damage is neutralised by mitophagy, thereby preventing cellular dysfunction and apoptosis. Mitophagy is the selective autophagy of mitochondria and has long been linked to age-dependent neurodegenerative disorders, including Parkinson’s and Alzheimer’s disease. . In cell-based systems and short-lived model organisms, mitophagy declines with age. However, the trajectories of mitophagy within the aging mammalian brain remain unexplored. We profiled mitophagy and macroautophagy within intact brain tissues using advanced genetically-encoded optical reporter mice. Methods: We an

…Mitochondrial dysfunction and oxidative stress are key players in ALS pathophysiology. Thus, improving mitochondrial function and/or antioxidant capacity constitute promising therapeutic strategies to delay ALS progression. We hypothesized that mitochondria-targeted antioxidant AntiOxCIN4 can reduce cardiac oxidative/nitrosative stress in SOD1G93A ALS mice

Arginase 2 (Arg2), an arginine-metabolizing, mitochondrial enzyme, has been recently found to be enriched in the striatum, and progressive loss of Arg2 has been proposed as a potential factor contributing to the pathogenesis of Huntington’s disease (HD), a disorder primarily involving this region of the brain. Although direct metabolic role of Arg2 is well established, the importance of this enzyme for striatal function and dysfunction is not known. The purpose of this work was to identify cellular pathways potentially controlled by Arg2 in the striatum. In our experiments, we have used wild-t

…Mitochondrial dysfunction is increasingly being recognized as an important factor contributing to the pathogenesis of ataxia. In particular, dysregulated mitochondrial fusion and fission events can now be regarded as pl

…stress has been associated with mitochondrial dysfunction, including impaired calcium homeostasis and elevated ROS production. However, the association between mitochondrial impairment and vascular function after TBI is poorly understood. We therefore aimed to 1) Identify the role of CSD on neurological outcome after TBI,

Oxidative stress and neuroinflammation are crucial phenomena in the pathogenesis of Alzheimer disease (AD). Oxotremorine-M (Oxo), a non-selective muscarinic acetylcholine receptors agonist, exerts neurotrophic functions in primary neurons and modulates oxidative stress and neuroinflammation phenomena in rat brain. Based on this, our study investigates Oxo positive effects on differentiated SH-SY5Y neuroblastoma cells, revealing that Oxo treatment a) enhances cell survival, b) increases neurite length and c) upregulates HSP70 and pHSF1 expression. Moreover, Oxo counteracts tert–Butyl hydroperox

Alterations along the brain-gut axis participate in the pathogenesis of neurodegenerative diseases. Recent data suggest that the gut microbiota partially exerts its action by modulating neuroinflammation. Interestingly, neuroinflammation has been postulated as one of the leading causes of Alzheimer’s Disease (AD). Therefore, targeting brain inflammation has been suggested as a promising therapeutic strategy to cope with AD. In this regard, neuroinflammation has been related to the soluble epoxide hydrolase (sEH) enzyme, which is upregulated in the brains of AD patients and mice models of AD. C

…possible convergence of ELS, AD and mitochondrial dysfunctions, utilizing proteomic analysis of synaptosomes​. Seeking to unde

Physiological levels of reactive oxygen species (ROS) are required for the proper regulation of biological functions and cell signaling. However, ROS overproduction and inadequate scavenging lead to oxidative stress and consequent damage to macromolecules. Recent evidence has demonstrated the incontrovertible involvement of oxidative stress in the onset and progression of different central nervous system (CNS) disorders, including neurodegenerative events. For instance, redox disbalance together with α-synuclein aggregation and neuroinflammation, contributes to the loss of dopaminergic neurons

…stress and a vicious cycle of mitochondrial damage, leading to apoptotic neuronal death. Pinocembrin (5,7-dihydroxyflavone), a major flavonoid found in honey and propolis, has shown significant neuroprotective property by suppressing Aβ cleaving enzyme in our previous study. The present study investigated a novel anti-AD effect of pinocembrin on mitochondrial dysfunction and apoptosis against Aβ injury. Neurotoxic

…Mitochondrial dysfunction and mitophagy defects are observed during senescence and AD, and studies suggest that they might lead to Aβ accumulation. Our goal in this project was to explore if a reduced removal of dysfunctional mitochondria during aging is a key contributor to amyloid pathology and