Evidence mapPaperPMID 42007396Full record

ReviewDrug design, development and therapy2026

Peptide-Based Therapeutics for Alzheimer's Disease: Medicinal Chemistry, AI-Guided Computational Design, and Blood-Brain Barrier Delivery.

Abdulaziz H Al Khzem, Mohamed S Gomaa

Abstract readReview
In one paragraph

Review in Drug design, development and therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

Abdulaziz H Al KhzemDepartment of Pharmaceutical Chemistry, College of Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Eastern Province, 31441, Kingdom of Saudi Arabia.ORCID 0009-0004-0079-8646
Mohamed S GomaaDepartment of Pharmaceutical Chemistry, College of Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Eastern Province, 31441, Kingdom of Saudi Arabia.ORCID 0000-0003-2112-9092

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alzheimer's disease (AD) represents a pressing challenge in modern medicine, with current therapeutics offering only symptomatic relief. Peptide-based therapeutics have emerged as promising candidates owing to their target specificity, favorable safety profiles, and ability to modulate protein-protein interactions inaccessible to small molecules. This narrative review evaluates medicinal chemistry and artificial intelligence (AI)-driven approaches that are reshaping peptide drug discovery for AD, spanning target selection, sequence design, synthesis optimization, and central nervous system (CNS) delivery. Peptides targeting key AD pathological mechanisms-including amyloid-β (Aβ) aggregation inhibition, tau hyperphosphorylation disruption, and neurotrophic signaling enhancement-are discussed alongside strategies such as cyclization, D-amino acid incorporation, PEGylation, and peptidomimetic design to improve metabolic stability and blood-brain barrier (BBB) penetration. We review automated fast-flow peptide synthesis with inline UV-vis monitoring as a platform for rapid, high-fidelity preparation of complex sequences suitable for translational development. Delivery platforms-including cell-penetrating peptides, intranasal formulations, and nanocarrier systems-which primarily increase systemic exposure or fundamentally alter CNS distribution mechanisms are presented. AI and machine-learning (ML) technologies, molecular simulations, and structure-prediction systems are examined as an integrated pipeline that supports end-to-end design, validation, and optimization, with emphasis on rigorous QSAR and docking/MD validation practices. Clinical translation is analyzed through peptide repurposing (e.g. GLP‑1 receptor agonists, intranasal insulin, oxytocin), dedicated peptide candidates, and evolving regulatory expectations. Finally, we outline concrete design checklists for CNS ready peptides, discuss key translational bottlenecks, and propose priorities for the next 5-10 years of peptide-based AD therapy development.

Indexed as

Alzheimer DiseaseArtificial IntelligenceBlood-Brain BarrierDrug Delivery SystemsDrug DesignPeptidesAnimalsChemistry, PharmaceuticalHumansPeptidesAlzheimer’s diseaseartificial intelligenceblood–brain barrierclinical translationdrug discoverypeptide drugspharmaceutical medicinal chemistry

Identifiers

PMID42007396
PMCPMC13089476

What Socratic holds

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LicenceCC BY-NC
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.