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2015: Which new directions for Alzheimer's disease?

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195350 Year: Pages: 122 DOI: 10.3389/978-2-88919-535-0 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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Abstract

According to the World Health Organization, more than 40 million people in the world are affected with dementia. To date, 60-70% of the cases of dementia are attributed to the Alzheimer's disease (AD). This neurodegenerative disorder gradually takes place over a period of at least 20 years before the onset of symptoms, which are impaired memory, apathy and depression. The characteristics of AD consist in neurofibrillary tangles (intraneuronal aggregates of hyperphosphorylated tau proteins) and senile plaques (dense extraneuronal deposits composed of amyloid ß (Aß)). The other features linked to these two core pathological hallmarks of AD are inflammation, oxidative stress, progressive synaptic and neuronal loss. In past years, some of the emerging therapeutic strategies against AD were employed to deal with the pathological hallmarks of the disease. Science teams all over the world try to restore the tau phosphorylation equilibrium. Their purpose is to interfere with the aggregation of tau and decrease its amount of proteins per se as well. Furthermore, they are trying either to stimulate the elimination processes of the aggregated tau proteins or to stop the formation of Aß peptides. This could be reached by the stimulation of the classic techniques of protein degradation such as the autophagic pathway, or by the targeted immunotherapy. In this Research Topic, we wish to summarize and review the etiology of AD and the related therapeutic opportunities for the next decades. To fully understand the precise mechanisms underlying AD, research findings, reviews, new insights and new approaches include AD and related tauopathies, tau phosphorylation balance, pharmacological compounds against AD, neuroprotection strategies and new therapeutic ways but also risk factors for AD and AD genetic information are included in this issue.

The Physiological Functions of the Amyloid Precursor Protein Gene Family

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453559 Year: Pages: 275 DOI: 10.3389/978-2-88945-355-9 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2018-02-27 16:16:45
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The amyloid precursor protein APP plays a key role in the pathogenesis of Alzheimer’s disease (AD), as proteolytical cleavage of APP gives rise to the Aß peptide which is deposited in the brains of Alzheimer patients. Despite this, our knowledge of the normal cell biological and physiological functions of APP and the closely related APLPs is limited. This may have hampered our understanding of AD, since evidence has accumulated that not only the production of the Aß peptide but also the loss of APP-mediated functions may contribute to AD pathogenesis. Thus, it appears timely and highly relevant to elucidate the functions of the APP gene family from the molecular level to their role in the intact organism, i.e. in the context of nervous system development, synapse formation and adult synapse function, as well as neural homeostasis and aging. Why is our understanding of the APP functions so limited? APP and the APLPs are multifunctional proteins that undergo complex proteolytical processing. They give rise to an almost bewildering array of different fragments that may each subserve specific functions. While Aß is aggregation prone and neurotoxic, the large secreted ectodomain APPsa - produced in the non-amyloidogenic a-secretase pathway - has been shown to be neurotrophic, neuroprotective and relevant for synaptic plasticity, learning and memory. Recently, novel APP cleavage pathways and enzymes have been discovered that have gained much attention not only with respect to AD but also regarding their role in normal brain physiology. In addition to the various cleavage products, there is also solid evidence that APP family proteins mediate important functions as transmembrane cell surface molecules, most notably in synaptic adhesion and cell surface signaling. Elucidating in more detail the molecular mechanisms underlying these divers functions thus calls for an interdisciplinary approach ranging from the structural level to the analysis in model organisms. Thus, in this research topic of Frontiers we compile reviews and original studies, covering our current knowledge of the physiological functions of this intriguing and medically important protein family.

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