The role of lysosomal cathepsins in neurodegeneration: Mechanistic insights, diagnostic potential and therapeutic approaches

Drobny A, Prieto Huarcaya S, Dobert J, Kluge A, Bunk J, Schlothauer T, Zunke F (2022)

Publication Type: Journal article, Review article

Publication year: 2022

Journal

Biochimica Et Biophysica Acta-Molecular Cell Research Elsevier

Book Volume: 1869

Article Number: 119243

Journal Issue: 7

DOI: 10.1016/j.bbamcr.2022.119243

Abstract

Lysosomes are ubiquitous organelles with a fundamental role in maintaining cellular homeostasis by mediating degradation and recycling processes. Cathepsins are the most abundant lysosomal hydrolyses and are responsible for the bulk degradation of various substrates. A correct autophagic function is essential for neuronal survival, as most neurons are post-mitotic and thus susceptible to accumulate cellular components. Increasing evidence suggests a crucial role of the lysosome in neurodegeneration as a key regulator of aggregation-prone and disease-associated proteins, such as α-synuclein, β-amyloid and huntingtin. Particularly, alterations in lysosomal cathepsins CTSD, CTSB and CTSL can contribute to the pathogenesis of neurodegenerative diseases as seen for neuronal ceroid lipofuscinosis, synucleinopathies (Parkinson's disease, Dementia with Lewy Body and Multiple System Atrophy) as well as Alzheimer's and Huntington's disease. In this review, we provide an overview of recent evidence implicating CTSD, CTSB and CTSL in neurodegeneration, with a special focus on the role of these enzymes in α-synuclein metabolism. In addition, we summarize the potential role of lysosomal cathepsins as clinical biomarkers in neurodegenerative diseases and discuss potential therapeutic approaches by targeting lysosomal function.

Authors with CRIS profile

Alice Drobny Department of Molecular Neurology Jan Dobert Department of Molecular Neurology Friederike Zunke Juniorprofessur für Translationale Neurowissenschaften

Involved external institutions

Christian-Albrechts-Universität zu Kiel DE Germany (DE)

How to cite

APA:

Drobny, A., Prieto Huarcaya, S., Dobert, J., Kluge, A., Bunk, J., Schlothauer, T., & Zunke, F. (2022). The role of lysosomal cathepsins in neurodegeneration: Mechanistic insights, diagnostic potential and therapeutic approaches. Biochimica Et Biophysica Acta-Molecular Cell Research, 1869(7). https://dx.doi.org/10.1016/j.bbamcr.2022.119243

MLA:

Drobny, Alice, et al. "The role of lysosomal cathepsins in neurodegeneration: Mechanistic insights, diagnostic potential and therapeutic approaches." Biochimica Et Biophysica Acta-Molecular Cell Research 1869.7 (2022).

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