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Emerging therapeutic potentials of dual-acting MAO and AChE inhibitors in Alzheimer's and Parkinson's diseases
Mathew B, Parambi DGT, Mathew GE, Uddin MS, Inasu ST, Kim H, Marathakam A, Unnikrishnan MK et al.. Archiv der Pharmazie, 2019-09-03
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
No drug has been approved to prevent neuronal cell loss in patients suffering from Parkinson's disease (PD) or Alzheimer's disease (AD); despite increased comprehension of the underlying molecular causes, therapies target cognitive functional improvement and motor fluctuation control. Drug design strategies that adopt the "one protein, one target" philosophy fail to address the multifactorial aetiologies of neurodegenerative disorders such as AD and PD optimally. On the contrary, restoring neurotransmitter levels by combined combinatorial inhibition of cholinesterases, monoamine oxidases, and adenosine A 2A A receptors, in conjunction with strategies to counter oxidative stress and beta-amyloid plaque accumulation, would constitute a therapeutically robust, multitarget approach. This extensive review delineates the therapeutic advantages of combining dual-acting molecules that inhibit monoamine oxidases and cholinesterases and/or adenosine A 2A A receptors, and describes the structure-activity relationships of compound classes that include, but are not limited to, alkaloids, coumarins, chalcones, donepezil-propargylamine conjugates, homoisoflavonoids, resveratrol analogs, hydrazones, and pyrazolines. In the wake of recent advances in network biology, in silico approaches, and omics, this review emphasizes the need to consider conceptually informed research strategies for drug discovery, in the context of the mounting burden posed by chronic neurodegenerative diseases with complex aetiologies and pathophysiologies involving multiple signalling pathways and numerous drug targets.
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APA 7th
Mathew, B., Parambi, D. G. T., Mathew, G. E., Uddin, M. S., Inasu, S. T., Kim, H., et al. (2019). Emerging therapeutic potentials of dual-acting MAO and AChE inhibitors in Alzheimer's and Parkinson's diseases. Archiv der Pharmazie. https://doi.org/10.1002/ardp.201900177
Vancouver
Mathew B, Parambi DGT, Mathew GE, Uddin MS, Inasu ST, Kim H, et al. Emerging therapeutic potentials of dual-acting MAO and AChE inhibitors in Alzheimer's and Parkinson's diseases. Archiv der Pharmazie. 2019. doi:10.1002/ardp.201900177. PMID: 31478569.
BibTeX
@article{mathew2019-31478569,
author = {Mathew, B. and Parambi, D. G. T. and Mathew, G. E. and Uddin, M. S. and Inasu, S. T. and Kim, H. and Marathakam, A. and Unnikrishnan, M. K. and others},
title = {{Emerging therapeutic potentials of dual-acting MAO and AChE inhibitors in Alzheimer's and Parkinson's diseases}},
journal = {Archiv der Pharmazie},
year = {2019},
doi = {10.1002/ardp.201900177},
pmid = {31478569},
url = {https://doi.org/10.1002/ardp.201900177}
}
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Key findings
- No drug has been approved to prevent neuronal cell loss in patients suffering from Parkinson's disease (PD) or Alzheimer's disease (AD); despite increased comprehension of the underlying molecular causes, therapies target cognitive functional improvement and motor fluctuation control.
- Drug design strategies that adopt the "one protein, one target" philosophy fail to address the multifactorial aetiologies of neurodegenerative disorders such as AD and PD optimally.
- On the contrary, restoring neurotransmitter levels by combined combinatorial inhibition of cholinesterases, monoamine oxidases, and adenosine A 2A A receptors, in conjunction with strategies to counter oxidative stress and beta-amyloid plaque accumulation, would constitute a therapeutically robust, multitarget approach.
- This extensive review delineates the therapeutic advantages of combining dual-acting molecules that inhibit monoamine oxidases and cholinesterases and/or adenosine A 2A A receptors, and describes the structure-activity relationships of compound classes that include, but are not limited to, alkaloids, coumarins, chalcones, donepezil-propargylamine conjugates, homoisoflavonoids, resveratrol analogs, hydrazones, and pyrazolines.
- In the wake of recent advances in network biology, in silico approaches, and omics, this review emphasizes the need to consider conceptually informed research strategies for drug discovery, in the context of the mounting burden posed by chronic neurodegenerative diseases with complex aetiologies and pathophysiologies involving multiple signalling pathways and numerous drug targets.
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Study details
- Evidence strengthLow
How this study scored 38/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 22 of the 58 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archiv der Pharmazie) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31478569) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 22 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 22 of the 58 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | — |
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