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Review
. 2020 Sep 14;40(19):e00262-20.
doi: 10.1128/MCB.00262-20. Print 2020 Sep 14.

Endosomal Trafficking in Alzheimer's Disease, Parkinson's Disease, and Neuronal Ceroid Lipofuscinosis

Yasir H Qureshi #  1 , Penelope Baez #  1 , Christiane Reitz  2   3   4   5
Affiliations
Review

Endosomal Trafficking in Alzheimer's Disease, Parkinson's Disease, and Neuronal Ceroid Lipofuscinosis

Yasir H Qureshi et al. Mol Cell Biol. .

Abstract

Neuronal ceroid lipofuscinosis (NCL) is one of the most prevalent neurodegenerative disorders of early life, Parkinson's disease (PD) is the most common neurodegenerative disorder of midlife, while Alzheimer's disease (AD) is the most common neurodegenerative disorder of late life. While they are phenotypically distinct, recent studies suggest that they share a biological pathway, retromer-dependent endosomal trafficking. A retromer is a multimodular protein assembly critical for sorting and trafficking cargo out of the endosome. As a lysosomal storage disease, all 13 of NCL's causative genes affect endolysosomal function, and at least four have been directly linked to retromer. PD has several known causative genes, with one directly linked to retromer and others causing endolysosomal dysfunction. AD has over 25 causative genes/risk factors, with several of them linked to retromer or endosomal trafficking dysfunction. In this article, we summarize the emerging evidence on the association of genes causing NCL with retromer function and endosomal trafficking, review the recent evidence linking NCL genes to AD, and discuss how NCL, AD, and PD converge on a shared molecular pathway. We also discuss this pathway's role in microglia and neurons, cell populations which are critical to proper brain homeostasis and whose dysfunction plays a key role in neurodegeneration.

Keywords: Alzheimer's disease (AD); NCL genes; Parkinson's disease; Vos29); Vps26; endocytic pathway; endosomal trafficking; genetic and cell biology findings on Alzheimer's disease; microglia; retromer defects; retromer proteins (Vps35; retromer viral vectors for AD gene therapy.

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References

    1. Lane CA, Hardy J, Schott JM. 2018. Alzheimer's disease. Eur J Neurol 25:59–70. doi:10.1111/ene.13439. - DOI - PubMed
    1. . 2020. Alzheimer's disease fact sheet. National Institute on Aging, Bethesda, MD.
    1. Cacace R, Sleegers K, Van Broeckhoven C. 2016. Molecular genetics of early-onset Alzheimer's disease revisited. Alzheimers Dement 12:733–748. doi:10.1016/j.jalz.2016.01.012. - DOI - PubMed
    1. Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. 2011. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med 1:a006189. doi:10.1101/cshperspect.a006189. - DOI - PMC - PubMed
    1. Braak H, Braak E. 1991. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259. doi:10.1007/BF00308809. - DOI - PubMed

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