The conversion of proteins from their native state into well-organized fibrillar aggregates underlies several human diseases, which can collectively be termed protein deposition diseases. Such pathological conditions include neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, as well as non-neuropathic conditions, such as systemic amyloidosis. These neurodegenerative diseases are marked by personality changes, memory loss (dementia), cognitive changes, blurred vision, insomnia, and loss of motor control. In certain diseases, protein aggregation occurs inside cells, whereas in others, protein deposition occurs in the extracellular space of the connective tissues and viscera, with the resulting protein aggregates generally termed amyloid fibrils. Despite substantial advances, these disorders are usually fatal or lead to serious debilitation and dramatic worsening of the quality of life.

As a result, there is a global concern to further elucidate the pathogenesis of such diseases and develop effective therapies. Significant progress made in elucidating molecular mechanisms that trigger the aggregation and the pathogenicity of proteins has enabled the design of novel and potentially powerful treatments. Nevertheless, little is known of the critical interactions in the complex in-vivo milieu which determines where and when protein deposition occurs in individual patients. Moreover, understanding of which molecular species are responsible for the pathogenesis is far from complete.

The acidic, 14-3-3 proteins abundantly expressed in the brain may be relevant to disease and have assumed significance as these are involved in age-related neurodegenerative diseases. More than 200 proteins are known to interact with the 14-3-3 protein family, including protein kinases, receptors, enzymes, structural and cytoskeletal proteins, small G-proteins, and their regulators, as well as proteins involved in scaffolding, cell cycle control, transcriptional regulation of gene expression, and apoptosis. Previous studies of invertebrates have demonstrated the importance of 14-3-3 proteins in the regulation of synaptic functions, learning, and memory. Nevertheless, the exact roles of 14-3-3 proteins in neurodegenerative diseases are far from being understood. Do 14-3-3 proteins have a direct role in memory loss? This vital question can be examined in animal models by making use of stem cell biology. Moreover, stem cells or Human Oligodendrocyte Precursor Cell-oligospheres (HOPC-os) can serve as therapeutic vehicles for transplantation purposes and regenerative therapies, e.g., for dementia. In the long term, such experiments should be able to contribute significantly both to understanding molecular mechanisms and eventually developing therapeutic strategies for those suffering from neurodegenerative diseases.

This Research Topic aims to collect Original Research, Reviews, Mini-Reviews, and perspectives on the advancement of 14-3-3 based therapeutic approaches in neurodegenerative disease. Areas of interest include but are not limited to, the following:

1. Isolation of Oligodendrocytes from the brain using animal models (rats, mice)
2. Isolation of 14-3-3 proteins and separation of different isoforms
3. Methods for transfer of cDNAs of 14-3-3 proteins into Human Oligodendrocyte Precursor Cell-oligospheres (HOPC-os)
4. Methods in transfer of 14-3-3 into stems cells isolated from human placenta
5. Transplantation of 14-3-3 functionalized oligospheres (Progenitor-Oligodendrocytes) into the brains of mice.
6. Identification of candidate molecules that interact with 14-3-3 proteins. Selection of best candidate molecules with potential for inhibiting 14-3-3 function both in vivo and in silico.

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Frontiers in Molecular Biosciences

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