[From gene to cell: Functional validation of RYR1 variants].

Genetic screening of rare diseases allows identification of the responsible gene(s) in about 50% of patients. The remaining cases are in a diagnostic deadlock as current knowledge fails to identify the correct gene or determine if the detected variant on the gene is pathogenic. These are named "variants of unknown significance" (VUS).

The Blood-Brain Barrier Is Unaffected in the Mouse Model of Leigh Syndrome.

Mitochondrial dysfunction plays a major role in physiological aging and in many pathological conditions. Yet, no study has explored the consequence of primary mitochondrial deficiency on the blood-brain barrier (BBB) structure and function. Addressing this question has major implications for pharmacological and genetic strategies aimed at ameliorating the neurological symptoms that are often predominant in patients suffering from these conditions.

Effect of Aβ Oligomers on Neuronal APP Triggers a Vicious Cycle Leading to the Propagation of Synaptic Plasticity Alterations to Healthy Neurons.

Alterations of excitatory synaptic function are the strongest correlate to the pathologic disturbance of cognitive ability observed in the early stages of Alzheimer's disease (AD). This pathologic feature is driven by amyloid-β oligomers (Aβos) and propagates from neuron to neuron. Here, we investigated the mechanism by which Aβos affect the function of synapses and how these alterations propagate to surrounding healthy neurons.

Gene replacement therapy provides benefit in an adult mouse model of Leigh syndrome.

Mutations in nuclear-encoded mitochondrial genes are responsible for a broad spectrum of disorders among which Leigh syndrome is the most common in infancy. No effective therapies are available for this severe disease mainly because of the limited capabilities of the standard adeno-associated viral (AAV) vectors to transduce both peripheral organs and the CNS when injected systemically in adults. Here, we used the brain-penetrating AAV-PHP.