Perspectives for treating Alzheimer's disease: a review on promising pharmacological substances

Abstract

CONTEXT AND OBJECTIVE: Dementia is a syndrome characterized by functional and cognitive decline. Alzheimer's disease (AD) is one of the most common causes of dementia and has high prevalence among the elderly. It is known that there is no drug capable of interfering with the course of the disease. Research on treatments for AD has been marked by the appearance of new drugs and their abandonment. This study aimed to describe drugs that have been studied with regard to treating AD and which are capable of influencing the course of the disease. DESIGN AND SETTING: Narrative review on original articles published worldwide. METHODS: A systematized search was conducted in the PubMed/MEDLINE, Cochrane Library/Cochrane and SciELO/Bireme databases. The descriptors "Molecular Mechanisms of Pharmacological Action" and "Drug Therapy" were each combined with the descriptor "Alzheimer disease". All of these can be found in MeSH and DeCS. These descriptors were used alone or in combination, and a filter specifying publication between January 2009 and October 2015 in English, Spanish or Portuguese was set. RESULTS: 6,888 articles were found, of which 37 were included in this review; 70.3% of the articles selected were of good quality with low or unclear risk of bias. 86 drugs were considered promising for AD treatment and these were classified into 20 pharmacological categories. CONCLUSION: There are no drugs capable of influencing the course of AD such that treatments are safe and effective. However, immunomodulators stood out as promising, given their effectiveness and quality in the articles analyzed. RESUMO CONTEXTO E OBJETIVO:A demência é uma síndrome caracterizada por declínio funcional e cognitivo, sendo a doença de Alzheimer (DA) uma das causas mais comuns e de alta prevalência em idosos. Sabe-se que não há medicamento capaz de interferir no curso da doença e as pesquisas para o tratamento da DA têm sido marcadas pelo surgimento e abandono de novas drogas. O objetivo deste estudo foi descrever as drogas capazes de influenciar o curso da DA que têm sido estudadas para o tratamento da doença.

Functional analyses of major cancer-related signaling pathways in Alzheimer's disease etiology

“…These unsatisfactory effects force people to pay attention on more targeted and etiology-oriented strategies [315]. Due to the notion that aging has been acknowledged as one of the major risk factors of AD pathogenesis [316], anti-aging drugs have become a promising therapeutic strategy against AD, which mainly occurs among the elderly population and features senescent phenotypes of affected neurons (Fig.…”

“…As mentioned above, multiple cellular signaling pathways are involved in the development of AD, which eventually converge to the formation of tau tangles and Aβ plaques [315]. There are three types of drugs that target specific signaling molecules in AD, including phosphodiesterase inhibitors, cyclin-dependent kinase 5 (CDK5) inhibitors and phospholipase A2 (PPA2) inhibitors [315].…”

“…There are three types of drugs that target specific signaling molecules in AD, including phosphodiesterase inhibitors, cyclin-dependent kinase 5 (CDK5) inhibitors and phospholipase A2 (PPA2) inhibitors [315]. First, the working mechanism of phosphodiesterase inhibitors is that they restrict the cellular transduction by down-regulating cAMP, that as a second messenger in neuron, further suppresses the expression of certain genes related to tau aggregation [335].…”

Alzheimer’s Disease: Molecular Hallmarks and Yeast Models

“…Current treatments are only useful in slowing down the progression of AD and helping patients manage some of their behavioral and cognitive symptoms instead of reversing the ultimate consequence [115]. These unsatisfactory effects force people to pay attention on more targeted and etiology-oriented strategies [116]. Due to the notion that age-related oxidative stress has been acknowledged as one of the major risk factors of AD pathogenesis and the early manifestation of AD [18], anti-aging drugs (antioxidants) have become the prevailing therapeutic strategy against AD.…”

Acetylcholinesterase: The “Hub” for Neurodegenerative Diseases and Chemical Weapons Convention

“…In case of donepezil, action on PAS is further regarded to reduce the biosynthesis of insoluble β-amyloid oligopeptides that bring about inflammatory response that contribute to the neurodegeneration characteristic of AD. Galantamine acts simultaneously as an AChE inhibitor and allosteric modulator of nicotinic receptors, increasing the affinity for ACh [114][115][116][117][118][119][120][121][122][123][124][125][126][127][128]. Research in progress on novel AD drugs has covered different disciplines and been focused on further development of AChE inhibitors, beta-secretase 1 (BACE-1) inhibitors, serotonin 5-HT 4 receptor inhibitors and PROTAC (PROteolysis Targeting Chimeras) compounds, among other approaches [129][130][131][132][133][134][135][136][137][138][139][140][141][142][143][144][145][146].…”