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| Content Provider | Springer Nature Link |
|---|---|
| Author | Teich, Andrew F. Nicholls, Russell E. Puzzo, Daniela Fiorito, Jole Purgatorio, Rosa Fa’, Mauro Arancio, Ottavio |
| Copyright Year | 2015 |
| Abstract | Therapeutic attempts to cure Alzheimer’s disease (AD) have failed, and new strategies are desperately needed. Motivated by this reality, many laboratories (including our own) have focused on synaptic dysfunction in AD because synaptic changes are highly correlated with the severity of clinical dementia. In particular, memory formation is accompanied by altered synaptic strength, and this phenomenon (and its dysfunction in AD) has been a recent focus for many laboratories. The molecule cyclic adenosine monophosphate response element-binding protein (CREB) is at a central converging point of pathways and mechanisms activated during the processes of synaptic strengthening and memory formation, as CREB phosphorylation leads to transcription of memory-associated genes. Disruption of these mechanisms in AD results in a reduction of CREB activation with accompanying memory impairment. Thus, it is likely that strategies aimed at these mechanisms will lead to future therapies for AD. In this review, we will summarize literature that investigates 5 possible therapeutic pathways for rescuing synaptic dysfunction in AD: 4 enzymatic pathways that lead to CREB phosphorylation (the cyclic adenosine monophosphate cascade, the serine/threonine kinases extracellular regulated kinases 1 and 2, the nitric oxide cascade, and the calpains), as well as histone acetyltransferases and histone deacetylases (2 enzymes that regulate the histone acetylation necessary for gene transcription). |
| Starting Page | 29 |
| Ending Page | 41 |
| Page Count | 13 |
| File Format | |
| ISSN | 19337213 |
| Journal | NeuroRX |
| Volume Number | 12 |
| Issue Number | 1 |
| e-ISSN | 18787479 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2015-01-10 |
| Publisher Institution | American Society for Experimental NeuroTherapeutics |
| Publisher Place | Boston |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | cAMP/PKA/CREB cascade Calpains NO cascade HAT HDAC ERK1/2 MAP kinase pathway Neurosciences Neurology Neurosurgery Neurobiology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neurology (clinical) Pharmacology Pharmacology (medical) |
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