scholarly journals Rationale for an anti‐inflammatory insulin sensitizer in a phase 3 Alzheimer's disease trial

2021 ◽  
Vol 17 (S9) ◽  
Author(s):  
Chris L Reading ◽  
Clarence N Ahlem ◽  
Narayanan Parameswaran
2020 ◽  
Vol 27 ◽  
Author(s):  
Reyaz Hassan Mir ◽  
Abdul Jalil Shah ◽  
Roohi Mohi-ud-din ◽  
Faheem Hyder Potoo ◽  
Mohd. Akbar Dar ◽  
...  

: Alzheimer's disease (AD) is a chronic neurodegenerative brain disorder characterized by memory impairment, dementia, oxidative stress in elderly people. Currently, only a few drugs are available in the market with various adverse effects. So to develop new drugs with protective action against the disease, research is turning to the identification of plant products as a remedy. Natural compounds with anti-inflammatory activity could be good candidates for developing effective therapeutic strategies. Phytochemicals including Curcumin, Resveratrol, Quercetin, Huperzine-A, Rosmarinic acid, genistein, obovatol, and Oxyresvertarol were reported molecules for the treatment of AD. Several alkaloids such as galantamine, oridonin, glaucocalyxin B, tetrandrine, berberine, anatabine have been shown anti-inflammatory effects in AD models in vitro as well as in-vivo. In conclusion, natural products from plants represent interesting candidates for the treatment of AD. This review highlights the potential of specific compounds from natural products along with their synthetic derivatives to counteract AD in the CNS.


2019 ◽  
Vol 16 (11) ◽  
pp. 1007-1017 ◽  
Author(s):  
James G. McLarnon

A combinatorial cocktail approach is suggested as a rationale intervention to attenuate chronic inflammation and confer neuroprotection in Alzheimer’s disease (AD). The requirement for an assemblage of pharmacological compounds follows from the host of pro-inflammatory pathways and mechanisms present in activated microglia in the disease process. This article suggests a starting point using four compounds which present some differential in anti-inflammatory targets and actions but a commonality in showing a finite permeability through Blood-brain Barrier (BBB). A basis for firstchoice compounds demonstrated neuroprotection in animal models (thalidomide and minocycline), clinical trial data showing some slowing in the progression of pathology in AD brain (ibuprofen) and indirect evidence for putative efficacy in blocking oxidative damage and chemotactic response mediated by activated microglia (dapsone). It is emphasized that a number of candidate compounds, other than ones suggested here, could be considered as components of the cocktail approach and would be expected to be examined in subsequent work. In this case, systematic testing in AD animal models is required to rigorously examine the efficacy of first-choice compounds and replace ones showing weaker effects. This protocol represents a practical approach to optimize the reduction of microglial-mediated chronic inflammation in AD pathology. Subsequent work would incorporate the anti-inflammatory cocktail delivery as an adjunctive treatment with ones independent of inflammation as an overall preventive strategy to slow the progression of AD.


2020 ◽  
Vol 20 (13) ◽  
pp. 1214-1234 ◽  
Author(s):  
Md. Tanvir Kabir ◽  
Md. Sahab Uddin ◽  
Bijo Mathew ◽  
Pankoj Kumar Das ◽  
Asma Perveen ◽  
...  

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the characteristics of this devastating disorder include the progressive and disabling deficits in the cognitive functions including reasoning, attention, judgment, comprehension, memory, and language. Objective: In this article, we have focused on the recent progress that has been achieved in the development of an effective AD vaccine. Summary: Currently, available treatment options of AD are limited to deliver short-term symptomatic relief only. A number of strategies targeting amyloid-beta (Aβ) have been developed in order to treat or prevent AD. In order to exert an effective immune response, an AD vaccine should contain adjuvants that can induce an effective anti-inflammatory T helper 2 (Th2) immune response. AD vaccines should also possess the immunogens which have the capacity to stimulate a protective immune response against various cytotoxic Aβ conformers. The induction of an effective vaccine’s immune response would necessitate the parallel delivery of immunogen to dendritic cells (DCs) and their priming to stimulate a Th2-polarized response. The aforesaid immune response is likely to mediate the generation of neutralizing antibodies against the neurotoxic Aβ oligomers (AβOs) and also anti-inflammatory cytokines, thus preventing the AD-related inflammation. Conclusion: Since there is an age-related decline in the immune functions, therefore vaccines are more likely to prevent AD instead of providing treatment. AD vaccines might be an effective and convenient approach to avoid the treatment-related huge expense.


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