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Neuroprotection by mitochondrial NAD against glutamate-induced excitotoxicity

Paiva, Bruna S.; Neves, Diogo; Tomé, Diogo; Costa, Filipa J.; Bruno, Inês C.; Trigo, Diogo; Silva, Raquel M.; Almeida, Ramiro D.

Excitotoxicity is a pathological process that occurs in many neurological diseases, such as stroke or epilepsy, and is characterized by the extracellular accumulation of high concentrations of glutamate or other excitatory amino acids (EAAs). Nicotinamide adenine dinucleotide (NAD) depletion is an early event following excitotoxicity in many in vitro and in vivo excitotoxic-related models and contributes to the...


Age-associated metabolic and epigenetic barriers during direct reprogramming of...

Santos, Francisco; Correia, Magda; Dias, Rafaela; Bola, Bárbara; Noberini, Roberta; Ferreira, Rita S.; Trigo, Diogo; Domingues, Pedro; Teixeira, José

Heart disease is the leading cause of mortality in developed countries, and novel regenerative procedures are warranted. Direct cardiac conversion (DCC) of adult fibroblasts can create induced cardiomyocytes (iCMs) for gene and cell-based heart therapy, and in addition to holding great promise, still lacks effectiveness as metabolic and age-associated barriers remain elusive. Here, by employing MGT (Mef2c, Gata...


Mitochondria dysfunction and impaired response to oxidative stress promotes pro...

Trigo, Diogo; Nadais, André; Carvalho, Ana; Morgado, Bárbara; Santos, Francisco; Nóbrega-Pereira, Sandrina; da Cruz E Silva, Odete A. B.

The plastic architecture of the mitochondrial network and its dynamic structure play crucial roles ensuring that varying energetic demands are rapidly met. Given the brain's high energy demand, mitochondria play a particularly critical role in neuronal and axonal energy homeostasis. With ageing physiological properties of the organism deteriorate, and are associated with loss of cellular homeostasis, accumulati...


Unravelling protein aggregation as an ageing related process or a neuropatholog...

Trigo, Diogo; Nadais, André; da Cruz E Silva, Odete A. B.

Protein aggregation is normally associated with amyloidosis, namely motor neurone, Alzheimer's, Parkinson's or prion diseases. However, recent results have unveiled a concept of gradual increase of protein aggregation associated with the ageing process, apparently not necessarily associated with pathological conditions. Given that protein aggregation is sufficient to activate stress-response and inflammation, i...


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