Enhanced expression of the autophagosomal marker LC3-II in detergent-resistant protein lysates from a CLN3 patient's post-mortem brain

Francesco Pezzini; Michele Fiorini; Stefano Doccini; Filippo Maria Santorelli; Gianluigi Zanusso; Alessandro Simonati

doi:10.1016/j.bbadis.2023.166756

Enhanced expression of the autophagosomal marker LC3-II in detergent-resistant protein lysates from a CLN3 patient's post-mortem brain

Biochim Biophys Acta Mol Basis Dis. 2023 Aug;1869(6):166756. doi: 10.1016/j.bbadis.2023.166756. Epub 2023 May 19.

Authors

Francesco Pezzini¹, Michele Fiorini², Stefano Doccini³, Filippo Maria Santorelli⁴, Gianluigi Zanusso⁵, Alessandro Simonati⁶

Affiliations

¹ Department of Surgery, Dentistry, Paediatrics and Gynaecology (Child Neurology and Psychiatry), University of Verona, 37134 Verona, Italy. Electronic address: francesco.pezzini@univr.it.
² Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona (Neuropathology Laboratory), 37134 Verona, Italy. Electronic address: michele.fiorini@univr.it.
³ Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit-IRCCS Stella Maris, 56128 Pisa, Italy. Electronic address: stefano.doccini@fsm.unipi.it.
⁴ Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit-IRCCS Stella Maris, 56128 Pisa, Italy. Electronic address: filippo3364@gmail.com.
⁵ Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona (Neuropathology Laboratory), 37134 Verona, Italy. Electronic address: gianluigi.zanusso@univr.it.
⁶ Department of Surgery, Dentistry, Paediatrics and Gynaecology (Child Neurology and Psychiatry), University of Verona, 37134 Verona, Italy. Electronic address: alessandro.simonati@univr.it.

PMID: 37209872
DOI: 10.1016/j.bbadis.2023.166756

Abstract

• Neuronal Ceroido Lipofuscinoses (NCL) are inherited, neurodegenerative disorders associated with lysosomal storage. • Impaired autophagy plays a pathogenetic role in several NCL forms, including CLN3 disease, but study on human brains are lacking. • In post-mortem brain samples of a CLN3 patient the LC3-I to LC3-II shift was consistent with activated autophagy. However, the autophagic process seemed to be ineffective due to the presence of lysosomal storage markers. • After fractionation with buffers of increasing detergent-denaturing strength, a peculiar solubility pattern of LC3-II was observed in CLN3 patient's samples, suggesting a different lipid composition of the membranes where LC3-II is stacked.

Keywords: Autophagy markers; Differential detergent fractioning; Human brain; LC3B; Lysosomal storage; Neuronal ceroid Lipofuscinoses (CLN3 disease).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain / metabolism
Detergents / pharmacology
Humans
Lysosomal Storage Diseases* / pathology
Membrane Glycoproteins / metabolism
Molecular Chaperones / metabolism
Neuronal Ceroid-Lipofuscinoses* / metabolism

Substances

Detergents
Membrane Glycoproteins
Molecular Chaperones
CLN3 protein, human