About this Research Topic
The progressive increase in the life expectancy of the world population is not necessarily related to an increase in the quality of life of individuals. Many times, it is associated with the appearance of neurodegenerative diseases. These can cause a decline in the memory, thinking, and behavior of the individual. Some provoke alterations in gait and movement or induce weakness and muscle atrophy. Others can cause pain, fatigue, tremor, lack of balance and limitations in language. These alterations are due to the progressive and irreversible degeneration of the Central Nervous System, which leads to the death of specific cell populations and contribute significantly to the morbidity and mortality of individuals.
The causes of such disorders are multifactorial, that is, several agents can determine their occurrence. They can be affected by external components such as alcoholism, infections, exposure to toxins or chemicals, the appearance of a tumor or a vascular event. Only, around 5-10% of people with a neurodegenerative disease have some type of mutation in specific genes. For example, mutations in APP, PS1, and PS2 genes, are associated with early-onset Alzheimer's disease (EOAD), variations in HTT gene are the cause of Huntington's disease, whereas mutations in the LRRK2, SNCA, PARK7, PARK2 or PINK1 genes remain linked with Parkinson's disease. In the same way, mutations in the NOTCH3 gene, have been related to hereditary vascular dementia.
Moreover, neurodegenerative diseases are characterized by the abnormal accumulation of proteins in the extracellular and intracellular space. These aggregates affect cell function, inducing neuronal death. Additionally, mitochondrial dysfunction is present, which leads to energy impairment, as well as, overproduction of unstable molecules such as free radicals, favoring oxidative stress (OS); which in turn interferes with protein function by oxidation and modification of protein structure. These alterations, eventually lead to disturbances in signaling pathways, a loss in the synaptic connections, as well as in the neuroglial interaction, which in turn contributes to decaying in the neuronal plasticity.
Another approach to explaining the neurodegeneration is related to gene expression, and epigenetic DNA modifications, deficiency in growth hormone or insulin–insulin-like growth factor I signaling, protein misfolding and neuroinflammation.
Neurodegenerative diseases are a whole of complex syndromes that affect millions of people throughout the world. Although in most cases, the risk increases considerably with age, there is a subgroup of pathologies that can occur in young people such as epilepsy, multiple sclerosis, and amyotrophic lateral sclerosis. Even though treatments can help mitigate some of the physical or mental symptoms, there is no real cure. For this reason, it is essential to understand the genetic and molecular mechanisms associated with these pathologies, which allow the development of new prevention and treatment strategies.
The aim of this Research Topic is to contribute to the understanding of:
• the main molecular processes that occur in the brain,
• how these are affected by genetics, behavior and the environment,
• the approach of new therapeutic strategies.
Keywords: Neurodegeneration, Oxidative stress, Dementia, Reactive Oxygen Species, Neuronal Plasticity, Epigenetic
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