Gabriele Siciliano

A novel mitochondrial tRNAPhe mutation causes MERRF syndrome.

A woman with typical features of myoclonic epilepsy with ragged red fibers (MERRF) had a novel heteroplasmic mutation (G611A) in the mitochondrial DNA tRNA phenylalanine gene. The mutation was heteroplasmic (91%) in muscle but undetectable in accessible tissues from the patient and her maternal relatives. Single-fiber PCR analysis showed that the proportion of mutant genomes was higher in cytochrome c oxidase (COX)-negative ragged red fibers (RRFs) than in COX-positive non-RRFs. This report shows that typical MERRF syndrome is not always associated with tRNA lysine mutations.

Mitochondrial DNA sequence variation and neurodegeneration

Mitochondria, the powerhouse of the cell, play a critical role in several metabolic processes and apoptotic pathways. Many lines of evidence suggest that mitochondria have a central role in ageing-related neurodegenerative diseases. Moreover, there is a long history of investigations on mitochondria aimed at identifying genetic markers relating to ageing and neurodegenerative diseases. In this review, some of the major neurodegenerative disorders are highlighted and the role of mitochondrial haplogroups in the pathogenetic cascade leading to these diseases is discussed.

Amyotrophic Lateral Sclerosis: A Genetic Point Of View.

In the last twenty years the rapid advances in neurogenetic have revolutionized not only the molecular, pathological, inheritance but also the clinical concept of ALS. Here we review the current genetic breakthrough in familial and sporadic ALS, considering how this knowledge has allowed widening of the scenario on the possible pathogenic disease mechanisms and better understanding of the relationship between the genetic, pathological and clinical subtypes.

Nrf2 Signaling: An Adaptive Response Pathway for Neurodegenerative Disorders

Oxidative damage contributes to pathogenesis in many neurodegenerative diseases. As the indicator and regulator of oxidative stress, the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway has been shown to have dynamic changes and examined for its neuroprotective role in many cases. Nrf2 is emerging as a regulatory protein in neuronal death, since it helps neuronal cells to meet with oxidative insults. In this chapter, we summarize the role of Nrf2 as a master regulator of oxidative stress. Furthermore, we treat some natural and chemical substances able to modulate the Nrf2 pathway and, therefore, their possible use in the neurodegenerative diseases therapeutic treatment.

The indistinct borders between psychological motivation, self-esteem, stress response and pain underline this assumption.

The current legal regime distinguishes between different types and categories of data. In general, the more personal, private and sensitive data are, the higher the level of protection provided. Among others, the legal regime differentiates between non-personal data and personal data, between metadata and content data and between nonsensitive and sensitive personal data. But there are at least three reasons why these legal categories may become redundant in the age of Big Data, artificial intelligence and increasing computational power.