Current Pharmaceutical Design - Volume 17, Issue 31, 2011

Several sporadic neurodegenerative diseases display phenomena that directly or indirectly relate to mitochondrial function. Data suggesting altered mitochondrial function in these diseases could arise from mitochondrial DNA (mtDNA) are reviewed. Approaches for manipulating mitochondrial function and minimizing the downstream consequences of mitochondrial dysfunction are discussed.

Mitochondrial dynamics play a crucial role in the pathobiology underlying Alzheimer's disease (AD) and Parkinson's disease (PD). Although a complete scientific understanding of these devastating conditions has yet to be realized, alterations in mitochondrial fission and fusion, and in the protein complexes that orchestrate mitochondrial fission and fusion, have been well established in AD- and PD-related neurodegeneratio Read More

Mitochondria fulfill a number of essential cellular functions, being recognized that the strict regulation of the structure, function and turnover of these organelles is an immutable control node for the maintenance of neuronal integrity and homeostasis. Many lines of evidence posit that mitochondria constitute a convergence point of preconditioning - a paradigm that affords robust brain tolerance in the face of neurodeg Read More

During the past decades, we have witnessed significant advances in our understanding of the molecular etiology of Parkinson's disease (PD). The unearthing of the causative genes for hereditary PD accelerated not only the studies of the molecular mechanisms underlying this pathology, but also set mitochondria at the center of PD pathology. In this review we revisit mitochondrial key role and propose a hypothesis for PD, tha Read More

Epigenetic alterations have been associated with several human diseases including Alzheimer's disease (AD). AD is a complex neurodegenerative disease characterized by a progressive decline in cognitive functions, neuronal cell loss and by the presence of β amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) in the cortex. Mutations in specific genes have been identified but can only explain a small percentage of th Read More

This review focuses on the discovery of activity-dependent neuroprotective protein (ADNP) and the ensuing discovery of NAP (davunetide) toward clinical development with emphasis on microtubule protection. ADNP immunoreactivity was shown to occasionally decorate microtubules and ADNP silencing inhibited neurite outgrowth as measured by microtubule associated protein 2 (MAP2) labeling. ADNP knockout is lethal, while 5 Read More

Aging is the major known risk factor for the onset of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Mitochondria play a central role in aging as mitochondrial dysfunction increases with age and produces harmful levels of reactive oxygen species which leads to cellular oxidative stress (free-radical theory of aging). Oxidative stress is highly damaging to cellular macromolecules and Read More

Alzheimer's and Parkinson's diseases represent the most prevalent neurodegenerative disorders worldwide. Current pharmacological or surgical treatments provide symptomatic benefits, particularly in the early stages, but none can delay or stop the progression of these diseases. There is an urgent need for new therapies able to modify disease progression. Gene therapy, mainly based on viral vectors, is presently being assu Read More

Cellular homeostasis relies on quality control systems so that damaged biologic structures are either repaired or degraded and entirely replaced by newly formed proteins or even organelles. The clearance of dysfunctional cellular structures in long-lived postmitotic cells, like neurons, is essential to eliminate, per example, defective mitochondria, lipofuscin-loaded lysosomes and oxidized proteins. Short-lived proteins are degraded Read More

Iron is a redox active metal involved in the oxidation-reduction reactions and regulation of cell growth and differentiation. Iron is an integral part of many proteins and enzymes that maintains various physiological functions. Most of the human body's iron is contained in red blood cells. Despite iron being an abundant trace metal in food, millions of people worldwide suffer from anemia. Iron deficiency results in impaired producti Read More

Alzheimer's is a neurodegenerative disease with a complex and progressive pathological phenotype characterized first by hypometabolism and impaired mitochondrial bioenergetics followed by pathological burden. The progressive and multifaceted degenerative phenotype of Alzheimer's suggests that successful treatment strategies necessarily will be equally multi-faceted and disease stage specific. Traditional therapeutic Read More