{
  "abstract": "Protein misfolding, aggregation, and oxidative stress contribute to aging and numerous neurodegenerative diseases, including Alzheimer's disease. Although the αA-crystallin-derived mini-chaperone peptide suppresses protein aggregation, its therapeutic potential is limited by susceptibility to proteolytic degradation. Here, we synthesized a protease-resistant analog composed entirely of D-amino acids (D-MC-αA) and compared its biochemical and biological properties with those of the parent peptide (MC-αA). Chaperone activity was assessed using two aggregation-prone model proteins, antioxidant activity by inhibition of Cu 2+ -mediated oxidation of ascorbic acid, and proteolytic stability by enzymatic digestion followed by reverse-phase HPLC. Cytoprotective and membrane-protective activities were evaluated using melittin-induced cytotoxicity in retinal pigment epithelial cells and hemolysis of human red blood cells. Peptide uptake, lifespan, thermotolerance, and protection against amyloid-β toxicity were evaluated in Caenorhabditis elegans ( C . elegans ). D-MC-αA exhibited approximately threefold greater chaperone activity than MC-αA, completely resisted enzymatic degradation, and more effectively inhibited Cu 2+ -mediated ascorbic acid oxidation. Both peptides protected retinal cells against melittin-induced injury and reduced red blood cell hemolysis. The mini-chaperone was efficiently taken up by C . elegans, and both peptides significantly extended lifespan, enhanced thermotolerance, delayed amyloid-β-induced paralysis, and prolonged survival without adversely affecting feeding behavior or reproduction. D-MC-αA provided greater protection than MC-αA against amyloid-β-induced paralysis and mortality. Collectively, these findings demonstrate that all-D-amino acid substitution confers proteolytic resistance, enhances chaperone and antioxidant activities, and preserves cytoprotective function, supporting further development of D-MC-αA for disorders associated with protein misfolding, oxidative stress, and amyloid toxicity.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Ophthalmology, University of Missouri, Columbia, MO 65212.",
    "Department of Biochemistry, University of Missouri, Columbia, MO 65212."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Swati Srivastava"
    },
    {
      "affs": [
        0
      ],
      "name": "Puttur Santhoshkumar"
    },
    {
      "affs": [
        0
      ],
      "name": "Tenzin Tender"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Krishna Sharma"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/apbzsxecesy10.bib",
  "cited_by": 0,
  "doi": "10.1016/j.freeradbiomed.2026.10.032",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13722526/",
  "id": "apbzsxecesy10",
  "issns": [
    "0891-5849",
    "1873-4596"
  ],
  "landing_url": "https://doi.org/10.1016/j.freeradbiomed.2026.10.032",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|Heat shock proteins research"
    ]
  ],
  "openalex": "W7221660534",
  "pdf_url": null,
  "pmcid": "PMC13722526",
  "pmid": "42869308",
  "published": "2026-10-13",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/apbzsxecesy10.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T12:23:00Z",
      "native_id": "PMC13722526",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.freeradbiomed.2026.10.032"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Heat shock proteins research",
      "subfield": "molecular-biology"
    }
  ],
  "title": "A protease-resistant D-amino acid αA-crystallin mini-chaperone with enhanced chaperone and antioxidant activities protects against amyloid-β proteotoxicity",
  "title_text": "A protease-resistant D-amino acid αA-crystallin mini-chaperone with enhanced chaperone and antioxidant activities protects against amyloid-β proteotoxicity",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:23:00Z",
  "url": "https://research.draconitic.com/paper/apbzsxecesy10",
  "venue": "Free radical biology & medicine",
  "versions": []
}