4.6 Article

Alzheimer's Disease Is Responsible for Progressive Age-Dependent Differential Expression of Various Protein Cascades in Retina of Mice

Journal

ACS CHEMICAL NEUROSCIENCE
Volume 10, Issue 5, Pages 2418-2433

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.8b00710

Keywords

Alzheimer's disease; retina; iTRAQ proteomics; biomarker discovery; aging

Funding

  1. National Natural Science Foundation of China [31750110473, 31870825, 21877081, 31470804]
  2. Shenzhen Bureau of Science, Technology, and Information [JCYJ20170412110026229, JCYJ20150529164656093, JSGG20140703163838793]

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Alzheimer's disease (AD) is a devastating neurodegenerative disease associated with cognitive impairments and memory loss usually in aged people. In the past few years, it has been detected in the eye retina, manifesting the systematic spread of the disease. This might be used for biomarker discovery for early detection and treatment of the disease. Here, we have described the proteomic alterations in retina of 2, 4, and 6 months old 3XTg-AD mice by using iTRAQ (isobaric tags for relative and absolute quantification) proteomics technology. Out of the total identified proteins, 121 (71 up- and 50 down-regulated), 79 (51 up- and 28 down-regulated), and 153 (37 up and 116 down-regulated) significantly differentially expressed proteins (DEPs) are found in 2, 4, and 6 month's mice retina (2, 4, and 6 M), respectively. Seventeen DEPs are found common in these three groups with consistent expression behavior or opposite expression in the three groups. Bioinformatics analysis of these DEPs highlighted their involvement in vital AD-related biological phenomenon. To further prompt the results, four proteins from 2 M group, three from 4 M, and four from 6 M age groups are successfully validated with Western blot analysis. This study confirms the retinal involvement of AD in the form of proteomic differences and further explains the protein-based molecular mechanisms, which might be a step toward biomarker discovery for early detection and treatment of the disease.

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