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NBIA Syndromes: A Step Forward from the Previous Knowledge.
Svetel, M, Dragašević, N, Petrović, I, Novaković, I, Tomić, A, Kresojević, N, Stanković, I, Kostić, V
Neurology India. 2021;(5):1380-1388
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Abstract
A disturbed iron metabolism may damage brain and trigger disorders known as neurodegeneration with brain iron accumulation (NBIA). NBIAs are rare, inherited disorders in which responsible mutations affect the function of proteins that participate in tissue iron homeostasis. Accumulated iron, which may be recognized as a low signal intensity on T2-weighted MRI images, oftentimes points to a diagnosis. Recent genetic discoveries confirm that NBIA is not a homogenous group of diseases. Fifteen different NBIAs have been described to date; among these, autosomal recessive inheritance was reported in 13, and autosmal dominant and X-linked dominant inheritance in one disease, respectively. Among NBIAs, the most common is pantothenate kinase-associated neurodegeneration (PKAN-NBIA 1) (30%-50% of all NBIA cases), that occurrs as a consequence of the autosomal recessive mutation in PANK2 gene, followed by phospholipase 2-associated neurodegeneration (PLAN, NBIA 2), due to mutation in PLA2G6 gene, and mitochondrial membrane protein-associated neurodegeneration (MPAN) with the underlying C19orf12 mutation [Table 1]. NBIAs are characterized by complex motor presentations from early-onset degeneration and premature fatality to adult-onset parkinsonism and dystonia. Epileptic seizures, pyramidal signs, visual disorders, and cognitive deterioration can develop. NBIAs are often refractory to therapeutical strategies, although certain interventions may provide significant symptomatic relief in selected patients. In this review, we discuss the expanding clinical spectrum of these complex and rare syndromes, their genetic and imaging features, and potential therapeutical targets and strategies.
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Therapeutic perspectives of epigenetically active nutrients.
Remely, M, Lovrecic, L, de la Garza, AL, Migliore, L, Peterlin, B, Milagro, FI, Martinez, AJ, Haslberger, AG
British journal of pharmacology. 2015;(11):2756-68
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Abstract
Many nutrients are known for a wide range of activities in prevention and alleviation of various diseases. Recently, their potential role in regulating human health through effects on epigenetics has become evident, although specific mechanisms are still unclear. Thus, nutriepigenetics/nutriepigenomics has emerged as a new and promising field in current epigenetics research in the past few years. In particular, polyphenols, as part of the central dynamic interaction between the genome and the environment with specificity at physiological concentrations, are well known to affect mechanisms underlying human health. This review summarizes the effects of dietary compounds on epigenetic mechanisms in the regulation of gene expression including expression of enzymes and other molecules responsible for drug absorption, distribution, metabolism and excretion in cancer, metabolic syndrome, neurodegenerative disorders and hormonal dysfunction.
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[Mechanisms of neurodegeneration in Alzheimer's disease].
Jovanović, Z
Medicinski pregled. 2012;(7-8):301-7
Abstract
INTRODUCTION Recent research into mechanisms of neurodegeneration in Alzheimer's disease has lead to a dramatic increase in our understanding of the mechanisms of cell death and neuroprotection. Alzheimer's disease is a complex disease with multiple etiological factors involved in disease pathogenesis. OXIDATIVE STRESS AND MITOCHONDRIAL DYSFUNCTION IN ALZHEIMER'S DISEASE Amyloid-beta peptide toxicity is mediated at least in part by oxidative stress. Anmyloid-beta peptide directly generates reactive oxygen species in the presence of redox-active metal ions. In Alzheimer's disease, oxidative stress is present early in pathogenesis and contributes to disease pathogenesis. Unlike other organs, the brain is especially vulnerable to reactive oxygen species due to neurons having relatively low levels of endogenous antioxidants. Overly abundant oxygen radicals cause the destruction of cellular macromolecules and participate in signaling mechanisms that result in apoptotic cell death. MICROGLIAL ACTIVATION AND NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE IN ALZHEIMER'S DISEASE There is a wealth of evidence demonstrating that microglia, the resident innate immune cells in the brain, can become deleterious and damage neurons. Microglial activation causes neuron damage through the production of neurotoxic factors, such as reactive oxygen species and cytokines that are toxic to neurons. The neuron also has strong homeostatic mechanisms that can delay or prevent activation of apoptosis and necrosis. INSULIN RESISTANCE AND ALZHEIMER'S DISEASE Insulin plays a role in Alzheimer's disease, as it is involved in the metabolism of beta-amyloid. Hyperinsulinemia and type-2 diabetes mellitus results in an increased risk of developing Alzheimer's disease, but its implications when the disease is already well established remain unknown. Treatment of central insulin resistance may be a promising avenue, not only in metabolic syndrom, but also in Alzheimer's disease. CONCLUSION Increasing evidence suggests a role for oxidative stress, mitochondrial dysfunction, microglial activation and insulin resistance in pathogenesis of neurodegenerative diseases including Alzheimer's disease.