Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
4.7
4.6
Journals
Pharmaceuticals
Special Issues
New Insights into Therapy for Alzheimer’s and Other Neurodegenerative Diseases
share announcement

New Insights into Therapy for Alzheimer’s and Other Neurodegenerative Diseases

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 22 June 2024 | Viewed by 8886

Special Issue Editors

Prof. Dr. Robert Joseph Shmookler Reis

E-Mail Website
Guest Editor
1. Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
2. Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA
Interests: Alzheimer’s disease; aging; determinants of longevity; neurodegenerative diseases
Dr. Meenakshisundaram Balasubramaniam

E-Mail Website
Guest Editor
Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
Interests: drug screening in silico; protein-protein interactions; bioinformatics
Dr. Srinivas Ayyadevara

E-Mail Website
Guest Editor
1. Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
2. Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA
Interests: Alzheimer’s disease; aging; determinants of longevity; neurodegenerative diseases; cardiovascular disease; cachexia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Alzheimer’s disease (AD) features two diagnostic types of aggregate: extracellular Aβ amyloids, and intra-neuronal tau tangles.  However, many other proteins have also been identified within AD aggregates and often feature AD-specific phosphorylations or other post-translational modifications [PTMs] 1,2.  The upregulation of several kinases has been implicated as possibly driving AD pathology, but other PTMs (e.g., acetylation, oxidation, glycosylation) can also induce protein misfolding and aggregation.  In this Special Issue of Pharmaceuticals, we welcome papers that describe research addressing any part of the progression from the identification of novel drug targets, the in silico screening of structural libraries, the validation of candidate molecules in cell or animal model systems, and ultimately culminating in human trials.  The highest priority will be given to work presenting novel targets and evidence for their potential utility in preventing or ameliorating Alzheimer’s disease or other neurological diseases, and any other diseases where protein aggregation due to altered proteostasis is noted, and to the identification and validation of early biomarkers associated with cognitive impairment and its progression to AD.

1   Ganne, A., Balasubramaniam, M., Griffin, W. S. T., Shmookler Reis, R. J. & Ayyadevara, S. Glial Fibrillary Acidic Protein: A Biomarker and Drug Target for Alzheimer's Disease. Pharmaceutics 14, doi:10.3390/pharmaceutics14071354 (2022).

2   Ayyadevara, S. et al. Proteins that mediate protein aggregation and cytotoxicity distinguish Alzheimer's hippocampus from normal controls. Aging Cell 15, 924-939, doi:10.1111/acel.12501 (2016).

Prof. Dr. Robert Joseph Shmookler Reis
Dr. Meenakshisundaram Balasubramaniam
Dr. Srinivas Ayyadevara
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Alzheimer’s disease
  • Parkinson’s disease
  • Huntington’s disease
  • amyotrophic lateral sclerosis
  • neurodegeneration
  • inflammation
  • anti-inflammatory drugs
  • post-translational modifications
  • protein misfolding
  • protein aggregation

Published Papers (3 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

13 pages, 1306 KiB  
Article
Nucleoside Reverse Transcriptase Inhibitor Exposure Is Associated with Lower Alzheimer’s Disease Risk: A Retrospective Cohort Proof-of-Concept Study
by Tiffany W. Chow, Mark Raupp, Matthew W. Reynolds, Siying Li, Gwendolyn E. Kaeser and Jerold Chun
Pharmaceuticals 2024, 17(4), 408; https://doi.org/10.3390/ph17040408 - 22 Mar 2024
Viewed by 3889
Abstract
Brain somatic gene recombination (SGR) and the endogenous reverse transcriptases (RTs) that produce it have been implicated in the etiology of Alzheimer’s disease (AD), suggesting RT inhibitors as novel prophylactics or therapeutics. This retrospective, proof-of-concept study evaluated the incidence of AD in people [...] Read more.
Brain somatic gene recombination (SGR) and the endogenous reverse transcriptases (RTs) that produce it have been implicated in the etiology of Alzheimer’s disease (AD), suggesting RT inhibitors as novel prophylactics or therapeutics. This retrospective, proof-of-concept study evaluated the incidence of AD in people with human immunodeficiency virus (HIV) with or without exposure to nucleoside RT inhibitors (NRTIs) using de-identified medical claims data. Eligible participants were aged ≥60 years, without pre-existing AD diagnoses, and pursued medical services in the United States from October 2015 to September 2016. Cohorts 1 (N = 46,218) and 2 (N = 32,923) had HIV. Cohort 1 had prescription claims for at least one NRTI within the exposure period; Cohort 2 did not. Cohort 3 (N = 150,819) had medical claims for the common cold without evidence of HIV or antiretroviral therapy. The cumulative incidence of new AD cases over the ensuing 2.75-year observation period was lowest in patients with NRTI exposure and highest in controls. Age- and sex-adjusted hazard ratios showed a significantly decreased risk for AD in Cohort 1 compared with Cohorts 2 (HR 0.88, p < 0.05) and 3 (HR 0.84, p < 0.05). Sub-grouping identified a decreased AD risk in patients with NRTI exposure but without protease inhibitor (PI) exposure. Prospective clinical trials and the development of next-generation agents targeting brain RTs are warranted. Full article
(This article belongs to the Special Issue New Insights into Therapy for Alzheimer’s and Other Neurodegenerative Diseases)
►▼ Show Figures

Graphical abstract

20 pages, 7352 KiB  
Article
Identification of Indazole-Based Thiadiazole-Bearing Thiazolidinone Hybrid Derivatives: Theoretical and Computational Approaches to Develop Promising Anti-Alzheimer’s Candidates
by Yousaf Khan, Shoaib Khan, Rafaqat Hussain, Wajid Rehman, Aneela Maalik, Urooba Gulshan, Mohamed W. Attwa, Hany W. Darwish, Hazem A. Ghabbour and Nawab Ali
Pharmaceuticals 2023, 16(12), 1667; https://doi.org/10.3390/ph16121667 - 30 Nov 2023
Cited by 2 | Viewed by 849
Abstract
A hybrid library of compounds based on indazole-based thiadiazole containing thiazolidinone moieties (1–17) was synthesized. The synthesized compounds were screened in vitro for their inhibition profile against targetedacetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities. All the derivatives demonstrated a varied [...] Read more.
A hybrid library of compounds based on indazole-based thiadiazole containing thiazolidinone moieties (1–17) was synthesized. The synthesized compounds were screened in vitro for their inhibition profile against targetedacetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities. All the derivatives demonstrated a varied range of inhibitory activities having IC50 values ranging from 0.86 ± 0.33 μM to 26.73 ± 0.84 μM (AChE) and 0.89 ± 0.12 μM to 27.08 ± 0.19 μM (BuChE), respectively. The results obtained were compared with standard Donepezil drugs (IC50 = 1.26 ± 0.18 μM for AChE) and (1.35 ± 0.37 μM for BuChE), respectively. Specifically, the derivatives 1–17, 1, 9, and 14 were found to be significantly active, with IC50 values of 0.86 ± 0.30, 0.92 ± 0.10, and 1.10 ± 0.37 μM (against AChE) and 0.89 ± 0.12, 0.98 ± 0.48 and 1.19 ± 0.42 μM (against BuChE), respectively.The structure–activity relationship (SAR) studies revealed that derivatives bearing para-CF3, ortho-OH, and para-F substitutions on the phenyl ring attached to the thiadiazole skeleton, as well as meta-Cl, -NO2, and para-chloro substitutions on the phenyl ring, having a significant effect on inhibitory potential. The synthesized scaffolds have been further characterized by using 1H-NMR, 13C-NMR, and (HR-MS) to confirm the precise structures of the synthesized compounds. Additionally, the molecular docking approach was carried out for most active compounds to explore the binding interactions established by most active compounds, with the active sites of targeted enzymes and obtained results supporting the experimental data. Full article
(This article belongs to the Special Issue New Insights into Therapy for Alzheimer’s and Other Neurodegenerative Diseases)
►▼ Show Figures

Figure 1

19 pages, 4350 KiB  
Article
Thiadiazolidinone (TDZD) Analogs Inhibit Aggregation-Mediated Pathology in Diverse Neurodegeneration Models, and Extend C. elegans Life- and Healthspan
by Samuel Kakraba, Srinivas Ayyadevara, Nirjal Mainali, Meenakshisundaram Balasubramaniam, Suresh Bowroju, Narsimha Reddy Penthala, Ramani Atluri, Steven W. Barger, Sue T. Griffin, Peter A. Crooks and Robert J. Shmookler Reis
Pharmaceuticals 2023, 16(10), 1498; https://doi.org/10.3390/ph16101498 - 20 Oct 2023
Viewed by 2080
Abstract
Chronic, low-grade inflammation has been implicated in aging and age-dependent conditions, including Alzheimer’s disease, cardiomyopathy, and cancer. One of the age-associated processes underlying chronic inflammation is protein aggregation, which is implicated in neuroinflammation and a broad spectrum of neurodegenerative diseases such as Alzheimer’s, [...] Read more.
Chronic, low-grade inflammation has been implicated in aging and age-dependent conditions, including Alzheimer’s disease, cardiomyopathy, and cancer. One of the age-associated processes underlying chronic inflammation is protein aggregation, which is implicated in neuroinflammation and a broad spectrum of neurodegenerative diseases such as Alzheimer’s, Huntington’s, and Parkinson’s diseases. We screened a panel of bioactive thiadiazolidinones (TDZDs) from our in-house library for rescue of protein aggregation in human-cell and C. elegans models of neurodegeneration. Among the tested TDZD analogs, PNR886 and PNR962 were most effective, significantly reducing both the number and intensity of Alzheimer-like tau and amyloid aggregates in human cell-culture models of pathogenic aggregation. A C. elegans strain expressing human Aβ1–42 in muscle, leading to AD-like amyloidopathy, developed fewer and smaller aggregates after PNR886 or PNR962 treatment. Moreover, age-progressive paralysis was reduced 90% by PNR886 and 75% by PNR962, and “healthspan” (the median duration of spontaneous motility) was extended 29% and 62%, respectively. These TDZD analogs also extended wild-type C. elegans lifespan by 15–30% (p < 0.001), placing them among the most effective life-extension drugs. Because the lead drug in this family, TDZD-8, inhibits GSK3β, we used molecular-dynamic tools to assess whether these analogs may also target GSK3β. In silico modeling predicted that PNR886 or PNR962 would bind to the same allosteric pocket of inactive GSK3β as TDZD-8, employing the same pharmacophore but attaching with greater avidity. PNR886 and PNR962 are thus compelling candidate drugs for treatment of tau- and amyloid-associated neurodegenerative diseases such as AD, potentially also reducing all-cause mortality. Full article
(This article belongs to the Special Issue New Insights into Therapy for Alzheimer’s and Other Neurodegenerative Diseases)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop