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Preclinical and clinical issues in Alzheimer's disease drug research and development

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194339 Year: Pages: 100 DOI: 10.3389/978-2-88919-433-9 Language: English
Publisher: Frontiers Media SA
Subject: Therapeutics --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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Abstract

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder characterized by progressive cognitive dysfunction and memory loss, inability to perform the activities of daily living and mood disorders. According to the so-called “amyloid cascade hypothesis”, amyloid-ß- peptide (Aß), produced by beta- and gamma- secretase-mediated cleavages of the amyloid precursor protein (APP), plays a pivotal role in the pathogenesis of AD. Aß was also shown to contribute to AD pathology by stimulating the hyperphosphorylation of tau which is responsible for the formation of neurofibrillary tangles. However, the “amyloid cascade hypothesis” was challenged by other theories which lend support to the idea that Aß is not causative but can be considered as an “innocent bystander” in AD. Although preclinical research generated impressive lines of evidence about the several intracellular mechanism(s) whose impairment leads to the onset and progression of AD, clinical research aimed at the development of new drugs capable of preventing or delaying the onset of neuronal damage in AD patients has produced limited results. The drugs currently available for the treatment of AD are acetylcholinesterase inhibitors (AChEI) and the NMDA glutamate receptor antagonist memantine. The AChEI increase acetylcholine levels in the synaptic cleft, which are reduced because of the progressive damage of cholinergic neurons in cognitive brain areas (e.g. amygdala, hippocampus, and frontal cortex), whereas memantine is used to prevent/reduce calcium-dependent excitotoxic neuronal cell death. Both classes of drugs have been shown to improve symptoms related to cognitive decline, but their effects are confined largely to patients with mild to moderate AD, in particular during the first year or so of treatment. An alternative to this symptomatic treatments involves the use of drugs that intervene in the pathogenesis of the disease. Recently, monoclonal antibodies against Aß were proposed as novel agents capable to remove Aß from the brain thus preventing neuronal damage. The research topic focuses on the preclinical and clinical evidence about the several factors that contribute to the pathogenesis of AD as well as the potential therapeutic role of new classes of drugs still under preclinical or clinical development.

Amyloid-beta clearance in Alzheimer's disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194438 Year: Pages: 111 DOI: 10.3389/978-2-88919-443-8 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-02-05 17:24:33
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Strong evidence continues to accumulate indicating that amyloid-beta (Aß) is a central part of Alzheimer’s disease (AD) pathogenesis in spite of the negative evidence coming from failed clinical trials. Therefore, mechanisms of clearance of Aß are of great interest in understanding AD pathogenesis and the development of effective treatments. This topic focuses on the issues related to Aß clearance in AD. The topics covered include proteases that degrade Aß and their localization, regulation, and functions. This topic also covers issues related to clearance through uptake by glia and through low-density lipoprotein (LDL) receptor mediated mechanisms. Signal transduction related to AD pathology and clearance is also addressed. Finally, immunotherapy and other novel therapeutic approaches are discussed.

Psychomotor symptomatology in psychiatric illnesses

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197255 Year: Pages: 137 DOI: 10.3389/978-2-88919-725-5 Language: English
Publisher: Frontiers Media SA
Subject: Psychiatry --- Medicine (General)
Added to DOAB on : 2016-04-07 11:22:02
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Psychomotor symptoms are those symptoms that are characterized by deficits in the initiation, execution and monitoring of movements, such as psychomotor slowing, catatonia, neurological soft signs (NSS), reduction in motor activity or extrapyramidal symptoms (EPS). These symptoms have not always received the attention they deserve although they can be observed in a wide range of psychiatric illnesses, including mood disorders, psychotic disorders, anxiety disorders, pervasive developmental disorders and personality disorders. Nevertheless, these symptoms seem to have prognostic value on clinical and functional outcome in several pathologies. In the late 19th century, the founding fathers of modern psychiatry (including Kahlbaum, Wernicke, Kraepelin and Bleuler) had a strong focus on psychomotor abnormalities in their description and definitions of psychiatric illnesses and systematically recognized these as core features of several psychiatric pathologies. Nevertheless, emphasis on these symptoms has reduced substantially since the emergence of psychopharmacology, given the association between antipsychotics or antidepressants and medication-induced motor deficits. This has resulted in the general idea that most if not all psychomotor deficits were merely side effects of their treatment rather than intrinsic features of the illness. Yet, the last two decades a renewed interest in these deficits can be observed and has yielded an exponential growth of research into these psychomotor symptoms in several psychiatric illnesses. This recent evolution is also reflected in the increased appreciation of these symptoms in the DSM-5. As a result of this increased focus, new insights into the clinical and demographical presentation, the etiology, the course, the prognostic value as well as treatment aspects of psychomotor symptomatology in different illnesses has emerged. Still, many new questions arise from these findings. This research topic is comprised of all types of contributions (original research, reviews, and opinion piece) with a focus on psychomotor symptomatology in a psychiatric illness, especially research focusing on one or more of the following topics: the clinical presentation of the psychomotor syndrome; the course through the illness; the diagnostical specificity of the syndrome; the underlying neurobiological or neuropsychological processes; new assessment techniques; pharmacological or non-pharmacological treatment strategies.

Im Leben bleiben

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Book Series: Gesellschaft der Unterschiede ISBN: 9783837629965 9783839429969 Year: DOI: 10.14361/9783839429969 Language: German
Publisher: transcript Verlag Grant: Knowledge Unlatched - 103343
Subject: Political Science
Added to DOAB on : 2018-03-30 11:01:58
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Wir werden immer älter. Gleichzeitig gibt es zunehmend Menschen, die mit Demenz altern und nur noch versorgt werden. Klar ist: Wir brauchen Alternativen zu den eingefahrenen Umgangsweisen. Was tun wir, um Orte zu schaffen, an denen wir Leben bleiben können - statt nur Leben? Wie können wir das Lebensumfeld von Menschen mit und ohne Demenz zu "menschenwärmenden Orten" machen? In Deutschland sind zahlreiche Initiativen im Aufbruch: Engagierte Menschen aus Politik, Kultur und Kirche sind auf kreative Weise unterwegs zu Demenzfreundlichen Kommunen. Die drei Autor/innen, eng vertraut mit dem Thema, zeigen Suchbewegungen, Stolpersteine und erste Lösungsansätze auf.

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