Topic: mitochondrial function

Alzheimer's disease (AD), the most common neurodegenerative dementia, involves Presenilins (PS) 1 and 2, which are pivotal in amyloid-β (Aβ) production and amyloid pathology. PS functions, associated with inherited AD (FAD), extend beyond Aβ production. PS2 in particular is critical in mitochondrial function and cell bioenergetics. Here, we aim to explore Presenilins' role in cellular lipid metabolism.Brain samples were collected from WT, PS2 +/-, PS2 -/- and PS2N141I mice, carrying the FAD N141I mutation. We evaluated LPL and nSMase 2 levels based on preliminary data indicating their upregula

Dopaminergic neuron cell death in Parkinson’s Disease (PD) is complex and combinatorial, with impairments in multiple cellular pathways impacting mitochondrial function, endosomal/lysosomal protein degradation, alpha-synuclein and tau aggregation, and neuroinflammation. Genetic risk factors, such as mutations in leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA), have been shown to impact kinetics of the autophagiclysosomal pathway (ALP), which is suggested to contribute to PD-associated protein accumulation and aggregation. Human-relevant in vitro models using patient-derived i

Disturbances to neuronal function at the level of the synapse are crucial features of neuropsychiatric disorders, such as schizophrenia. Synaptic dysfunction in the prefrontal cortex, and its consequences on neuronal circuitry and behaviour, have been extensively linked to the disease. In this study, we are characterising the functional and behavioural consequences of a recently discovered, schizophrenia-associated variant in the CACNG2 gene, coding for the postsynaptic protein stargazin (StgSCZ). The aim of our study is to uncover how dysfunction at the level of the synapse in the prefrontal

The complexity of neurodegenerative processes and the human nervous system hinder progress towards a comprehensive understanding of both. Much of our advancements in understanding disease has been through the use of human post-mortem tissues. As these are only representative of the end stage of life, it is difficult to differentiate between chronic long-term consequences of disease (ie, neurofibrillary tangles) and potential regulators which directly drive pathological processes. Using small animal model systems has limitations resulting in high failure to translate directly from rodent-derive

Circadian clocks, endogenous oscillators that synchronize biological processes with the environmental day-night cycle, are entrained by external cues, notably sunlight. However, this mechanism is remarkably diverse across species. Mammals exhibit a hierarchical circadian system centered around the suprachiasmatic nucleus, while fish present a more distributed system with tissues directly responding to sunlight. Through mRNA-sequencing and promoter analysis, we explored the cellular transcriptional response to sunlight in zebrafish (D. rerio) and blind cavefish (P. andruzzii), the latter servin

Second generation antipsychotics (SGAs) are the first line treatment for psychosis and schizophrenia. SGAs are efficacious in reducing symptoms of these neuropsychiatric conditions; however, they are associated with metabolic side-effects that can be detrimental to a patient’s health and well-being. Patient’s taking SGAs have a three-fold increased risk of developing metabolic syndrome (MetS). MetS includes the development of type 2 diabetes, unprecedented weight gain, and dyslipidaemia. We hypothesised that SGAs disrupt mitochondrial function in the brain and periphery, and this may explain t

Introduction: Major depressive disorder (MDD) is a prevalent, complex condition with an unclear pathophysiology. Studies have shown structural and cellular changes in the hippocampus and reduced synaptic density in the prefrontal cortex of depressed individuals (Kang HJ et al. Nature Medicine 2012;18(9):1413-1417). Additionally, impaired mitochondrial function has been linked to susceptibility to mental health disorders.Objectives: This study aimed to examine synaptic and mitochondrial characteristics in post-mortem hippocampal tissues, specifically in individuals with MDD.Methods: The three s

Translating insights from genome-wide association studies (GWASs) into practical therapies for depression poses a significant challenge. Our objective is to address this challenge by utilizing network-based algorithms on GWAS outcomes for drug repurposing. This approach aims to advance precision medicine, specifically focusing on East Asian populations.Our research involved an initial meta-analysis of GWASs to reveal genetic variants linked to depression, utilizing data from large-scale studies including the Taiwan Biobank (Ntotal: 19389) and BioBank Japan (Ntotal: 178630). We employed a rando