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Int. J. Mol. Sci. 2017, 18(8), 1806; doi:10.3390/ijms18081806

A Comparison of Lysosomal Enzymes Expression Levels in Peripheral Blood of Mild- and Severe-Alzheimer’s Disease and MCI Patients: Implications for Regenerative Medicine Approaches

1
Department of Chemistry, Biology and Biotechnology, Biochemistry and Molecular Biology Unit, University of Perugia, Perugia 06123, Italy
2
Department of Surgery and Biomedical Sciences, Section of Human, Clinical and Forensic Anatomy, School of Medicine, University of Perugia, Perugia 06132, Italy
3
Department of Aging Medical Science, University of G. d’Annunzio, Chieti e Pescara, Chieti 66100, Italy
4
Department of Medicine, Section of Cardiovascular, Endocrine and Metabolic Clinical Physiology and Laboratory for Endocrine Cell Transplants and Bio-hybrid Organs, University of Perugia, Perugia 06132, Italy
5
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona 37134, Italy
6
Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Roma, Roma 06100, Italy
*
Author to whom correspondence should be addressed.
Received: 7 July 2017 / Revised: 4 August 2017 / Accepted: 14 August 2017 / Published: 19 August 2017
(This article belongs to the Special Issue Nano/Micro-Assisted Regenerative Medicine)
View Full-Text   |   Download PDF [2039 KB, uploaded 22 August 2017]   |  

Abstract

The association of lysosomal dysfunction and neurodegeneration has been documented in several neurodegenerative diseases, including Alzheimer’s Disease (AD). Herein, we investigate the association of lysosomal enzymes with AD at different stages of progression of the disease (mild and severe) or with mild cognitive impairment (MCI). We conducted a screening of two classes of lysosomal enzymes: glycohydrolases (β-Hexosaminidase, β-Galctosidase, β-Galactosylcerebrosidase, β-Glucuronidase) and proteases (Cathepsins S, D, B, L) in peripheral blood samples (blood plasma and PBMCs) from mild AD, severe AD, MCI and healthy control subjects. We confirmed the lysosomal dysfunction in severe AD patients and added new findings enhancing the association of abnormal levels of specific lysosomal enzymes with the mild AD or severe AD, and highlighting the difference of AD from MCI. Herein, we showed for the first time the specific alteration of β-Galctosidase (Gal), β-Galactosylcerebrosidase (GALC) in MCI patients. It is notable that in above peripheral biological samples the lysosomes are more sensitive to AD cellular metabolic alteration when compared to levels of Aβ-peptide or Tau proteins, similar in both AD groups analyzed. Collectively, our findings support the role of lysosomal enzymes as potential peripheral molecules that vary with the progression of AD, and make them useful for monitoring regenerative medicine approaches for AD. View Full-Text
Keywords: β-Hexosaminidase; β-Galactosidase; β-Galactosylcebrosidase; β-Glucuronidase; Cathepsin S; Cathepsin D; Cathepsin B; Cathepsin L; dementia; neurodegeneration; aging β-Hexosaminidase; β-Galactosidase; β-Galactosylcebrosidase; β-Glucuronidase; Cathepsin S; Cathepsin D; Cathepsin B; Cathepsin L; dementia; neurodegeneration; aging
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Morena, F.; Argentati, C.; Trotta, R.; Crispoltoni, L.; Stabile, A.; Pistilli, A.; di Baldassarre, A.; Calafiore, R.; Montanucci, P.; Basta, G.; Pedrinolla, A.; Smania, N.; Venturelli, M.; Schena, F.; Naro, F.; Emiliani, C.; Rende, M.; Martino, S. A Comparison of Lysosomal Enzymes Expression Levels in Peripheral Blood of Mild- and Severe-Alzheimer’s Disease and MCI Patients: Implications for Regenerative Medicine Approaches. Int. J. Mol. Sci. 2017, 18, 1806.

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