Topic: SNCA

Preclinical research into dementia with Lewy bodies (DLB) is challenging due to the lack of α-synucleinopathy animal models that do not also develop Parkinsonism. To address this issue, we have developed a new mouse model for investigating the impact of α-synuclein (α-Syn) overexpression and aggregation on driving cortical and hippocampal circuit dysfunction. Using bilateral stereotaxic injections of adeno-associated virus (AAVs) vectors, we transduced overexpression of human SNCA (encoding α-Syn) with mScarlet (red fluorophore), or an mScarlet-only control vector. We targeted either dorsal hi

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

Parkinson’s disease (PD) is a debilitating neurodegenerative disorder and there is no cure to treat or prevent the disease. The cardinal motor symptoms of PD are caused by a decline of nerve cells producing the neurotransmitter dopamine, which is necessary for the initiation of voluntary movements, but other transmitter systems including the serotonin and norepinephrine systems are affected as well and are related to non-motor symptoms such as depression and dementia. On a pathological level, PD is also characterized by intracellular proteinaceous inclusions known as Lewy bodies that contain t

Parkinson’s disease (PD) is a progressive disorder of the nervous system, affecting 1% of the ageing population. Common motor symptoms include tremor and bradykinesia, while non-motor symptoms range from constipation to sleep disturbances. The neuropathological hallmarks involve the loss of dopaminergic neurons in the substantia nigra and abnormal intra-neuronal accumulation of Lewy bodies. Here, the zebrafish model is used to investigate the behavioural defects associated with PD. Mutations of PARK2, PINK1, PARK7, LRRK2 and SNCA genes cause different forms of PD in humans. Using CRISPR/Cas9