Synaptic Alterations in a Transgenic Model of Tuberous Sclerosis Complex: Relevance to Autism Spectrum Disorders.

Tuberous sclerosis complex (TSC) is a rare, multi-system genetic disease with serious neurological and mental symptoms, including autism. Mutations in the / genes lead to the overactivation of mTOR signalling, which is also linked to nonsyndromic autism. Our aim was to analyse synaptic pathology in a transgenic model of TSC: two-month-old male B6;129S4-Tsc2 mice with Tsc2 haploinsufficiency.

Age-Related Transcriptional Deregulation of Genes Coding Synaptic Proteins in Alzheimer's Disease Murine Model: Potential Neuroprotective Effect of Fingolimod.

Alzheimer's disease (AD) induces time-dependent changes in sphingolipid metabolism, which may affect transcription regulation and neuronal phenotype. We, therefore, analyzed the influence of age, amyloid β precursor protein (AβPP), and the clinically approved, bioavailable sphingosine-1-phosphate receptor modulator fingolimod (FTY720) on the expression of synaptic proteins. RNA was isolated, reverse-transcribed, and subjected to real-time PCR.

Exogenous Alpha-Synuclein Evoked Parkin Downregulation Promotes Mitochondrial Dysfunction in Neuronal Cells. Implications for Parkinson's Disease Pathology.

Aberrant secretion and accumulation of α-synuclein (α-Syn) as well as the loss of parkin function are associated with the pathogenesis of Parkinson's disease (PD). Our previous study suggested a functional interaction between those two proteins, showing that the extracellular α-Syn evoked post-translational modifications of parkin, leading to its autoubiquitination and degradation. While parkin plays an important role in mitochondrial biogenesis and turnover, including mitochondrial fission/fusion as well as mitophagy, the involvement of parkin deregulation in α-Syn-induced mitochondrial damage is largely unknown.

Dysfunctional proteins in neuropsychiatric disorders: From neurodegeneration to autism spectrum disorders.

Despite fundamental differences in disease course and outcomes, neurodevelopmental (autism spectrum disorders - ASD) and neurodegenerative disorders (Alzheimer's disease - AD and Parkinson's disease - PD) present surprising, common traits in their molecular pathomechanisms. Uncontrolled oligomerization and aggregation of amyloid β (Aβ), microtubule-associated protein (MAP) tau, or α-synuclein (α-syn) contribute to synaptic impairment and the ensuing neuronal death in both AD and PD. Likewise, the pathogenesis of ASD may be attributed, at least in part, to synaptic dysfunction; attention has also been recently paid to irregularities in the metabolism and function of the Aβ precursor protein (APP), tau, or α-syn.