New Discoveries in Drug Targets and Delivery for Alzheimer’s Disease

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: 30 October 2024 | Viewed by 10369

Special Issue Editors


E-Mail Website
Guest Editor
Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Im Neuenheimer Feld 329, D-69120 Heidelberg, Germany
Interests: CNS drug delivery; blood–brain barrier; CNS pharmacokinetics; intra-brain delivery; membrane transporters
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Im Neuenheimer Feld 329, D-69120 Heidelberg, Germany
Interests: CNS drug delivery; blood–brain barrier; glia–neuron interactions; brain physiopathology

Special Issue Information

Dear Colleagues,

Alzheimer’s Disease (AD), the most common cause of dementia, affects over 40 million people worldwide. The situation is expected to intensify in the coming years, with devastating social and economic effects. Despite intensive clinical research efforts, there are currently no treatments or effective preventive strategies for AD. In fact, FDA-approved drugs only relieve symptoms. The main reasons for AD treatment’s failure are the multifactorial and heterogeneous physiopathological mechanisms of the disease, erroneous selection of drug targets, lack of relevant animal models, and obstacles in drug delivery into the brain due to the high selectivity of the blood–brain barrier, which limits the access of therapeutic agents into the central nervous system.

Therefore, this Special Issue aims to collect original research articles and reviews with the most relevant and innovative findings in the field of AD. Manuscripts dealing with new targets and therapeutic strategies, pharmaceutical formulations, and drug delivery systems as well as relevant models used for the development of effective AD treatments are of great interest.

We look forward to receiving your contributions.

Dr. Elena Puris
Dr. Sabrina Petralla
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. Pharmaceutics 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
  • therapeutic strategies
  • drug delivery
  • drug targets
  • blood–brain barrier
  • animal models

Published Papers (3 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Review

23 pages, 1905 KiB  
Review
Therapeutic Strategies Aimed at Improving Neuroplasticity in Alzheimer Disease
by María F. Colavitta and Francisco J. Barrantes
Pharmaceutics 2023, 15(8), 2052; https://doi.org/10.3390/pharmaceutics15082052 - 31 Jul 2023
Cited by 2 | Viewed by 2170
Abstract
Alzheimer disease (AD) is the most prevalent form of dementia among elderly people. Owing to its varied and multicausal etiopathology, intervention strategies have been highly diverse. Despite ongoing advances in the field, efficient therapies to mitigate AD symptoms or delay their progression are [...] Read more.
Alzheimer disease (AD) is the most prevalent form of dementia among elderly people. Owing to its varied and multicausal etiopathology, intervention strategies have been highly diverse. Despite ongoing advances in the field, efficient therapies to mitigate AD symptoms or delay their progression are still of limited scope. Neuroplasticity, in broad terms the ability of the brain to modify its structure in response to external stimulation or damage, has received growing attention as a possible therapeutic target, since the disruption of plastic mechanisms in the brain appear to correlate with various forms of cognitive impairment present in AD patients. Several pre-clinical and clinical studies have attempted to enhance neuroplasticity via different mechanisms, for example, regulating glucose or lipid metabolism, targeting the activity of neurotransmitter systems, or addressing neuroinflammation. In this review, we first describe several structural and functional aspects of neuroplasticity. We then focus on the current status of pharmacological approaches to AD stemming from clinical trials targeting neuroplastic mechanisms in AD patients. This is followed by an analysis of analogous pharmacological interventions in animal models, according to their mechanisms of action. Full article
Show Figures

Figure 1

26 pages, 6172 KiB  
Review
New Insights into Alzheimer’s Disease: Novel Pathogenesis, Drug Target and Delivery
by Haishu Chen, Jinan Xu, Hanyuan Xu, Tiancheng Luo, Yihao Li, Ke Jiang, Yangping Shentu and Zhiqian Tong
Pharmaceutics 2023, 15(4), 1133; https://doi.org/10.3390/pharmaceutics15041133 - 3 Apr 2023
Cited by 2 | Viewed by 3156
Abstract
Alzheimer’s disease (AD), the most common type of dementia, is characterized by senile plaques composed of amyloid β protein (Aβ) and neurofilament tangles derived from the hyperphosphorylation of tau protein. However, the developed medicines targeting Aβ and tau have not obtained ideal clinical [...] Read more.
Alzheimer’s disease (AD), the most common type of dementia, is characterized by senile plaques composed of amyloid β protein (Aβ) and neurofilament tangles derived from the hyperphosphorylation of tau protein. However, the developed medicines targeting Aβ and tau have not obtained ideal clinical efficacy, which raises a challenge to the hypothesis that AD is Aβ cascade-induced. A critical problem of AD pathogenesis is which endogenous factor induces Aβ aggregation and tau phosphorylation. Recently, age-associated endogenous formaldehyde has been suggested to be a direct trigger for Aβ- and tau-related pathology. Another key issue is whether or not AD drugs are successfully delivered to the damaged neurons. Both the blood–brain barrier (BBB) and extracellular space (ECS) are the barriers for drug delivery. Unexpectedly, Aβ-related SP deposition in ECS slows down or stops interstitial fluid drainage in AD, which is the direct reason for drug delivery failure. Here, we propose a new pathogenesis and perspectives on the direction of AD drug development and drug delivery: (1) aging-related formaldehyde is a direct trigger for Aβ assembly and tau hyperphosphorylation, and the new target for AD therapy is formaldehyde; (2) nano-packaging and physical therapy may be the promising strategy for increasing BBB permeability and accelerating interstitial fluid drainage. Full article
Show Figures

Graphical abstract

17 pages, 593 KiB  
Review
Physiologic Functions and Therapeutic Applications of α7 Nicotinic Acetylcholine Receptor in Brain Disorders
by Chien-Hsing Lee and Shih-Ya Hung
Pharmaceutics 2023, 15(1), 31; https://doi.org/10.3390/pharmaceutics15010031 - 22 Dec 2022
Cited by 9 | Viewed by 3868
Abstract
Accumulating data suggest that α7 nicotinic acetylcholine receptors (α7nAChRs) are an important therapeutic target for the treatment of Alzheimer’s disease (AD) and schizophrenia. The homopentameric ligand-gated ion channel α7nAChR consists of five identical α7 subunits that are encoded by the CHRNA7 (cholinergic receptor [...] Read more.
Accumulating data suggest that α7 nicotinic acetylcholine receptors (α7nAChRs) are an important therapeutic target for the treatment of Alzheimer’s disease (AD) and schizophrenia. The homopentameric ligand-gated ion channel α7nAChR consists of five identical α7 subunits that are encoded by the CHRNA7 (cholinergic receptor nicotinic alpha7 subunit) gene. Moreover, α7nAChRs are densely distributed throughout the hippocampus, cortex, and thalamus brain regions, but sparsely in the striatum, forebrain, and medulla. Compared with other nAChRs, α7nAChR binds with low affinity to the naturally occurring neurotransmitter acetylcholine and the non-specific exogenous agonist nicotine, and with high affinity to the specific antagonists α-bungarotoxin and methyllycaconitine. Reports indicate that α7nAChR plays important roles in neurotransmitter release, cognitive functioning, and the cholinergic anti-inflammatory response. Genetic variations that alter CHRNA7 mRNA and protein expression or cause α7nAChR dysfunction are associated with many brain disorders. Our previous studies revealed that α7nAChR exerts neuroprotection in AD by acting as a cargo receptor for binding the autophagosomal marker protein LC3 and engulfing extracellular neurotoxic Aβ1–42 during autophagic degradation of the α7nAChR-Aβ1–42 complex. However, the role of α7nAChRs in other diseases remains unknown. Here, we review and summarize the essential characteristics and current findings concerning α7nAChRs in four common brain diseases (AD, Parkinson’s disease, schizophrenia, and depression), which may elucidate the role of α7nAChRs and inform innovative research and novel treatments that target α7nAChRs in brain disease. Full article
Show Figures

Figure 1

Back to TopTop