Multi-target design strategies for the improved treatment of Alzheimer's disease

Zhang, Pengfei; Xu, Shengtao; Zhu, Zheying; Xu, Jinyi

doi:10.1016/j.ejmech.2019.05.020

Cited by 156 publications

(90 citation statements)

References 124 publications

(116 reference statements)

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“…Thus, therapeutic strategies against free radical damage, protein oxidation, calcium and free radicals, tau and Aβ deposits, and phosphorylation may aid in the prevention of stroke-induced acceleration of dementia [175,176].…”

Section: Other Mechanismsmentioning

confidence: 99%

From Stroke to Dementia: a Comprehensive Review Exposing Tight Interactions Between Stroke and Amyloid-β Formation

Goulay

Romo

Hol

et al. 2019

Transl. Stroke Res.

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Stroke and Alzheimer's disease (AD) are cerebral pathologies with high socioeconomic impact that can occur together and mutually interact. Vascular factors predisposing to cerebrovascular disease have also been specifically associated with development of AD, and acute stroke is known to increase the risk to develop dementia. Despite the apparent association, it remains unknown how acute cerebrovascular disease and development of AD are precisely linked and act on each other. It has been suggested that this interaction is strongly related to vascular deposition of amyloid-β (Aβ), i.e., cerebral amyloid angiopathy (CAA). Furthermore, the blood-brain barrier (BBB), perivascular space, and the glymphatic system, the latter proposedly responsible for the drainage of solutes from the brain parenchyma, may represent key pathophysiological pathways linking stroke, Aβ deposition, and dementia. In this review, we propose a hypothetic connection between CAA, stroke, perivascular space integrity, and dementia. Based on relevant pre-clinical research and a few clinical case reports, we speculate that impaired perivascular space integrity, inflammation, hypoxia, and BBB breakdown after stroke can lead to accelerated deposition of Aβ within brain parenchyma and cerebral vessel walls or exacerbation of CAA. The deposition of Aβ in the parenchyma would then be the initiating event leading to synaptic dysfunction, inducing cognitive decline and dementia. Maintaining the clearance of Aβ after stroke could offer a new therapeutic approach to prevent post-stroke cognitive impairment and development into dementia.

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Section: Other Mechanismsmentioning

confidence: 99%

From Stroke to Dementia: a Comprehensive Review Exposing Tight Interactions Between Stroke and Amyloid-β Formation

Goulay

Romo

Hol

et al. 2019

Transl. Stroke Res.

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show abstract

“…AD is a central nervous system degenerative disease that seriously threatens the health of the elderly. Modern pharmacological studies have shown that common pathological features of AD include β-amyloid (Aβ) plaques, excessive phosphorylation of Tau protein to form neurofibrillary tangles, reduction of acetylcholine transmitters and inflammatory responses, and neuronal loss [34,35].…”

Section: Pharmacological Effects Of Pinocembrinmentioning

confidence: 99%

Advances in Biosynthesis, Pharmacology, and Pharmacokinetics of Pinocembrin, a Promising Natural Small-Molecule Drug

et al. 2019

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Pinocembrin is one of the most abundant flavonoids in propolis, and it may also be widely found in a variety of plants. In addition to natural extraction, pinocembrin can be obtained by biosynthesis. Biosynthesis efficiency can be improved by a metabolic engineering strategy and a two-phase pH fermentation strategy. Pinocembrin poses an interest for its remarkable pharmacological activities, such as neuroprotection, anti-oxidation, and anti-inflammation. Studies have shown that pinocembrin works excellently in treating ischemic stroke. Pinocembrin can reduce nerve damage in the ischemic area and reduce mitochondrial dysfunction and the degree of oxidative stress. Given its significant efficacy in cerebral ischemia, pinocembrin has been approved by China Food and Drug Administration (CFDA) as a new treatment drug for ischemic stroke and is currently in progress in phase II clinical trials. Research has shown that pinocembrin can be absorbed rapidly in the body and easily cross the blood–brain barrier. In addition, the absorption/elimination process of pinocembrin occurs rapidly and shows no serious accumulation in the body. Pinocembrin has also been found to play a role in Parkinson’s disease, Alzheimer’s disease, and specific solid tumors, but its mechanisms of action require in-depth studies. In this review, we summarized the latest 10 years of studies on the biosynthesis, pharmacological activities, and pharmacokinetics of pinocembrin, focusing on its effects on certain diseases, aiming to explore its targets, explaining possible mechanisms of action, and finding potential therapeutic applications.

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“…Other combinations were found to be effective in metal chelating activity and antioxidant properties with less toxicity [237,239]. Similarly, combinations of AChE with GSK3β inhibitors, MAO inhibitors, metal chelators, NMDAR inhibitors, 5-HT receptor inhibitors, histaminic receptors inhibitors and phosphodiesterase inhibitors have been studied [240]. Some drugs designed in this way have been reported to alleviate AD.…”

Section: Drug Combinations As a Strategy For Ad Therapymentioning

confidence: 99%

Dietary Polyphenols: A Multifactorial Strategy to Target Alzheimer’s Disease

Dhakal

Kushairi

Phan

et al. 2019

IJMS

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Ageing is an inevitable fundamental process for people and is their greatest risk factor for neurodegenerative disease. The ageing processes bring changes in cells that can drive the organisms to experience loss of nutrient sensing, disrupted cellular functions, increased oxidative stress, loss of cellular homeostasis, genomic instability, accumulation of misfolded protein, impaired cellular defenses and telomere shortening. Perturbation of these vital cellular processes in neuronal cells can lead to life threatening neurological disorders like Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease, Lewy body dementia, etc. Alzheimer’s Disease is the most frequent cause of deaths in the elderly population. Various therapeutic molecules have been designed to overcome the social, economic and health care burden caused by Alzheimer’s Disease. Almost all the chemical compounds in clinical practice have been found to treat symptoms only limiting them to palliative care. The reason behind such imperfect drugs may result from the inefficiencies of the current drugs to target the cause of the disease. Here, we review the potential role of antioxidant polyphenolic compounds that could possibly be the most effective preventative strategy against Alzheimer’s Disease.

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Multi-target design strategies for the improved treatment of Alzheimer's disease

Cited by 156 publications

References 124 publications

From Stroke to Dementia: a Comprehensive Review Exposing Tight Interactions Between Stroke and Amyloid-β Formation

From Stroke to Dementia: a Comprehensive Review Exposing Tight Interactions Between Stroke and Amyloid-β Formation

Advances in Biosynthesis, Pharmacology, and Pharmacokinetics of Pinocembrin, a Promising Natural Small-Molecule Drug

Dietary Polyphenols: A Multifactorial Strategy to Target Alzheimer’s Disease

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