Amyloid cascade in Alzheimer's disease: Recent advances in medicinal chemistry

Mohamed, Tarek; Shakeri, Arash; Rao, Praveen P.N.

doi:10.1016/j.ejmech.2016.02.049

Cited by 163 publications

(132 citation statements)

References 109 publications

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“…Accumulation of the β-amyloid peptide (Aβ) in brain tissues represents the pathological status of AD [9,10]. According to the amyloid hypothesis, disruption of homeostatic processes causes overproduction of Aβ.…”

Section: Current Therapy To Treat Alzheimer´s Disease (Ad)mentioning

confidence: 99%

“…According to the amyloid hypothesis, disruption of homeostatic processes causes overproduction of Aβ. Age-related factors could favor a metabolic alteration, favoring the amyloidogenic processing [9,10]. The neurotoxic potential of the Aβ results from its potential to favor aggregation.…”

Section: Current Therapy To Treat Alzheimer´s Disease (Ad)mentioning

confidence: 99%

“…This process, along with a reduction of Aβ removal from the brain, leads to the extracellular accumulation of Aβ, and the subsequent activation of neurotoxic cascades, that ultimately leads to neuronal dysfunction and cellular death [9,10]. The relevance of the early diagnosis of AD relies on the hypothesis that pharmacological interferences on diseasemodifying complexes are more likely to produce clinically relevant rules if started early enough in the continuum towards dementia [9,10]. Therapies leading the change of amyloid-related cascades may be viewed as promising plans to attenuate or even to revert dementia [10].…”

Section: Current Therapy To Treat Alzheimer´s Disease (Ad)mentioning

confidence: 99%

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Pharmacological modulation of neural Ca2+/camp signaling interaction as therapeutic goal for treatment of Alzheimer´s disease

Caricati‐Neto¹,

Bergantin²

2017

J Syst Integr Neurosci

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Alzheimer's disease (AD) is a debilitating neuropsychiatric disorder characterized by the multifaceted decline in cognitive and behavioral functions. Due to the multifaceted nature of AD pathology and our limited understanding on its etiology, AD is difficult to be treated with currently available pharmaceuticals. Then, new therapeutic strategies for AD have been proposed. Since 1975, several clinical studies have reported that L-type Ca 2+ channel blockers (CCBs) used in antihypertensive therapy produces increase of plasma catecholamine levels and tachycardia, typical symptoms of sympathetic hyperactivity. Despite these adverse effects of CCBs have been initially attributed to adjust reflex of arterial pressure, during almost four decades these enigmatic phenomena remained unclear. In 2013, we discovered that this paradoxical sympathetic hyperactivity produced by CCBs results from the increase of catecholamines release from sympathetic nerves and adrenal chromaffin cells due to its modulatory action on the interaction between intracellular signaling pathways mediated by Ca 2+ and cAMP (Ca 2+ /cAMP signalling interaction). In addition, we discovered that the modulation of this interaction may stimulate neuroprotective response due to activation of cell survival pathways mediated by cAMP-responsive element binding protein (CREB). Then, the pharmacological modulation of Ca 2+ /cAMP signalling interaction by combined use of L-type CCBs and cAMP-enhancer compounds could be a more efficient and safer therapeutic strategy to produce increase of cholinergic neurotransmission and neuroprotection, attenuating cognitive deficit in AD patients.

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Section: Current Therapy To Treat Alzheimer´s Disease (Ad)mentioning

confidence: 99%

Section: Current Therapy To Treat Alzheimer´s Disease (Ad)mentioning

confidence: 99%

Section: Current Therapy To Treat Alzheimer´s Disease (Ad)mentioning

confidence: 99%

See 1 more Smart Citation

Pharmacological modulation of neural Ca2+/camp signaling interaction as therapeutic goal for treatment of Alzheimer´s disease

Caricati‐Neto¹,

Bergantin²

2017

J Syst Integr Neurosci

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“…The amyloid aggregates spark a sequence of events that lead to AD development including neuronal injury and synaptic loss. It is generally accepted that brain β-amyloid deposition is relatively diffuse, and there is non-linear correlation between the density of mature Aβ aggregate and severity of AD, which denotes that soluble Aβ oligomers per se are neurotoxic and cause synaptic dysfunction even in the absence of insoluble aggregate [11,12].…”

Section: The Amyloid Hypothesismentioning

confidence: 99%

Sex Hormones and Alzheimer’s Disease

Bahnasy¹,

El-Heneedy²,

El-Seidy³

2018

Sex Hormones in Neurodegenerative Processes and Diseases

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Alzheimer's disease (AD) is the most common type of dementia and the most common neurodegenerative disorder of elderly. It is not an accelerated form of aging but it is characterized by distinct temporospatial brain pathological changes, including amyloid plaques accumulation, neurofibrillary tangles deposition, synaptic loss and neuronal death with gross brain atrophy. These changes result in persistent progressive memory and cognitive decline interfering with the usual daily activities. AD is a multifactorial disorder results from the interaction of genetic, epigenetic, environmental and lifestyle factors. Estrogen, progesterone and androgen effects are important building stones in AD pathogenesis, and their effect in brain modulation and development results in different gender susceptibility to the disease. These sex hormones whether gonadal or neurosteroids (synthesized locally in the brain) play important neuroprotective roles influencing the individual's vulnerability to AD development, rate of mild cognitive impairment (MCI)/AD conversion and speed of AD progression. Despite the little therapeutic implications of hormonal replacement therapy in AD treatment, yet this topic still represents a challenging hopeful way to construct a strategy for the development of personalized, gender-specific AD management.

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“…Small derivatives have been developed that are able to interfere with Aβ aggregation by decreasing the oligomerization process and/ or by inducing a conformational change in β-sheet assembly and/or by inducing quick conversion of soluble aggregates into less toxic fibrils (Table 3) [1,41].…”

Section: Aβ Aggregation Inhibitormentioning

confidence: 99%