The Ups and Downs of BACE1: Walking a Fine Line between Neurocognitive and Other Psychiatric Symptoms of Alzheimer's Disease
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- Aβ, Nrg1/ErbB signaling, demyelination, neuregulin, neurodegenerative disease, peptide, synaptic plasticity,
- MeSH
- Alzheimer Disease * MeSH
- Amyloid beta-Peptides MeSH
- Aspartic Acid Endopeptidases MeSH
- Humans MeSH
- Amyloid Precursor Protein Secretases * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Amyloid beta-Peptides MeSH
- Aspartic Acid Endopeptidases MeSH
- BACE1 protein, human MeSH Browser
- Amyloid Precursor Protein Secretases * MeSH
Although neurocognitive deficit is the best-recognized indicator of Alzheimer's disease (AD), psychotic and other noncognitive symptoms are the prime cause of institutionalization. BACE1 is the rate-limiting enzyme in the production of Aβ of AD, and one of the promising therapeutic targets in countering cognitive decline and amyloid pathology. Changes in BACE1 activity have also emerged to cause significant noncognitive neuropsychiatric symptoms and impairments of circadian rhythms, as evident from clinical trials and reports in transgenic models. In this study, we consider key characteristics of BACE1 with its contribution to neurocognitive deficit and other psychiatric symptoms of AD. We argue that a growing list of noncognitive mental impairments related to pharmacological modulation of BACE1 might present a major obstacle in clinical translation of emerging therapeutic leads targeting this protease. The adverse effects of BACE1 inhibition on mental health call for a revision of treatment strategies that assume indiscriminate inhibition of this key protease, and stress the need for further mechanistic and translational studies.
Department of Medical Genetics 3rd Faculty of Medicine Charles University Prague Czech Republic
International Centre for Neurotherapeutics Dublin City University Dublin Ireland
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