Disruption of the Autophagy-Lysosome Pathway is Involved in Neuropathology of the nclf Mouse Model of Neuronal Ceroid Lipofuscinosis

Thelen M, Damme M, Schweizer M, Hagel C, Wong A, Cooper JD, Braulke T, Galliciotti G (2012)
PLOS ONE 7(4): e35493.

Download
Es wurde kein Volltext hochgeladen. Nur Publikationsnachweis!
Zeitschriftenaufsatz | Veröffentlicht | Englisch
Autor
; ; ; ; ; ; ;
Abstract / Bemerkung
Variant late-infantile neuronal ceroid lipofuscinosis, a fatal lysosomal storage disorder accompanied by regional atrophy and pronounced neuron loss in the brain, is caused by mutations in the CLN6 gene. CLN6 is a non-glycosylated endoplasmic reticulum (ER)-resident membrane protein of unknown function. To investigate mechanisms contributing to neurodegeneration in CLN6 disease we examined the nclf mouse, a naturally occurring model of the human CLN6 disease. Prominent autofluorescent and electron-dense lysosomal storage material was found in cerebellar Purkinje cells, thalamus, hippocampus, olfactory bulb and in cortical layer II to V. Another prominent early feature of nclf pathogenesis was the localized astrocytosis that was evident in many brain regions and the more widespread microgliosis. Expression analysis of mutant Cln6 found in nclf mice demonstrated synthesis of a truncated protein with a reduced half-life. Whereas the rapid degradation of the mutant Cln6 protein can be inhibited by proteasomal inhibitors, there was no evidence for ER stress or activation of the unfolded protein response in various brain areas during postnatal development. Age-dependent increases in LC3-II, ubiquitinated proteins, and neuronal p62-positive aggregates were observed, indicating a disruption of the autophagy-lysosome degradation pathway of proteins in brains of nclf mice, most likely due to defective fusion between autophagosomes and lysosomes. These data suggest that proteasomal degradation of mutant Cln6 is sufficient to prevent the accumulation of misfolded Cln6 protein, whereas lysosomal dysfunction impairs constitutive autophagy promoting neurodegeneration.
Erscheinungsjahr
Zeitschriftentitel
PLOS ONE
Band
7
Zeitschriftennummer
4
Seite
e35493
ISSN
eISSN
PUB-ID

Zitieren

Thelen M, Damme M, Schweizer M, et al. Disruption of the Autophagy-Lysosome Pathway is Involved in Neuropathology of the nclf Mouse Model of Neuronal Ceroid Lipofuscinosis. PLOS ONE. 2012;7(4):e35493.
Thelen, M., Damme, M., Schweizer, M., Hagel, C., Wong, A., Cooper, J. D., Braulke, T., et al. (2012). Disruption of the Autophagy-Lysosome Pathway is Involved in Neuropathology of the nclf Mouse Model of Neuronal Ceroid Lipofuscinosis. PLOS ONE, 7(4), e35493. doi:10.1371/journal.pone.0035493
Thelen, M., Damme, M., Schweizer, M., Hagel, C., Wong, A., Cooper, J. D., Braulke, T., and Galliciotti, G. (2012). Disruption of the Autophagy-Lysosome Pathway is Involved in Neuropathology of the nclf Mouse Model of Neuronal Ceroid Lipofuscinosis. PLOS ONE 7, e35493.
Thelen, M., et al., 2012. Disruption of the Autophagy-Lysosome Pathway is Involved in Neuropathology of the nclf Mouse Model of Neuronal Ceroid Lipofuscinosis. PLOS ONE, 7(4), p e35493.
M. Thelen, et al., “Disruption of the Autophagy-Lysosome Pathway is Involved in Neuropathology of the nclf Mouse Model of Neuronal Ceroid Lipofuscinosis”, PLOS ONE, vol. 7, 2012, pp. e35493.
Thelen, M., Damme, M., Schweizer, M., Hagel, C., Wong, A., Cooper, J.D., Braulke, T., Galliciotti, G.: Disruption of the Autophagy-Lysosome Pathway is Involved in Neuropathology of the nclf Mouse Model of Neuronal Ceroid Lipofuscinosis. PLOS ONE. 7, e35493 (2012).
Thelen, Melanie, Damme, Markus, Schweizer, Michaela, Hagel, Christian, Wong, Andrew, Cooper, Jonathan D., Braulke, Thomas, and Galliciotti, Giovanna. “Disruption of the Autophagy-Lysosome Pathway is Involved in Neuropathology of the nclf Mouse Model of Neuronal Ceroid Lipofuscinosis”. PLOS ONE 7.4 (2012): e35493.

26 Zitationen in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

Murine knockin model for progranulin-deficient frontotemporal dementia with nonsense-mediated mRNA decay.
Nguyen AD, Nguyen TA, Zhang J, Devireddy S, Zhou P, Karydas AM, Xu X, Miller BL, Rigo F, Ferguson SM, Huang EJ, Walther TC, Farese RV., Proc Natl Acad Sci U S A 115(12), 2018
PMID: 29511098
Lysosomes and Brain Health.
Sharma J, di Ronza A, Lotfi P, Sardiello M., Annu Rev Neurosci 41(), 2018
PMID: 29661037
Loss of CLN7 results in depletion of soluble lysosomal proteins and impaired mTOR reactivation.
Danyukova T, Ariunbat K, Thelen M, Brocke-Ahmadinejad N, Mole SE, Storch S., Hum Mol Genet 27(10), 2018
PMID: 29514215
Retinal Degeneration In A Mouse Model Of CLN5 Disease Is Associated With Compromised Autophagy.
Leinonen H, Keksa-Goldsteine V, Ragauskas S, Kohlmann P, Singh Y, Savchenko E, Puranen J, Malm T, Kalesnykas G, Koistinaho J, Tanila H, Kanninen KM., Sci Rep 7(1), 2017
PMID: 28487519
Dysregulation of autophagy as a common mechanism in lysosomal storage diseases.
Seranova E, Connolly KJ, Zatyka M, Rosenstock TR, Barrett T, Tuxworth RI, Sarkar S., Essays Biochem 61(6), 2017
PMID: 29233882
Lysosomal dysfunction and impaired autophagy in a novel mouse model deficient for the lysosomal membrane protein Cln7.
Brandenstein L, Schweizer M, Sedlacik J, Fiehler J, Storch S., Hum Mol Genet 25(4), 2016
PMID: 26681805
Autophagy in neuronal cells: general principles and physiological and pathological functions.
Damme M, Suntio T, Saftig P, Eskelinen EL., Acta Neuropathol 129(3), 2015
PMID: 25367385
Autophagy in the physiology and pathology of the central nervous system.
Nikoletopoulou V, Papandreou ME, Tavernarakis N., Cell Death Differ 22(3), 2015
PMID: 25526091
HRES-1/Rab4 promotes the formation of LC3(+) autophagosomes and the accumulation of mitochondria during autophagy.
Talaber G, Miklossy G, Oaks Z, Liu Y, Tooze SA, Chudakov DM, Banki K, Perl A., PLoS One 9(1), 2014
PMID: 24404161
Gene disruption of Mfsd8 in mice provides the first animal model for CLN7 disease.
Damme M, Brandenstein L, Fehr S, Jankowiak W, Bartsch U, Schweizer M, Hermans-Borgmeyer I, Storch S., Neurobiol Dis 65(), 2014
PMID: 24423645
Deregulation of subcellular biometal homeostasis through loss of the metal transporter, Zip7, in a childhood neurodegenerative disorder.
Grubman A, Lidgerwood GE, Duncan C, Bica L, Tan JL, Parker SJ, Caragounis A, Meyerowitz J, Volitakis I, Moujalled D, Liddell JR, Hickey JL, Horne M, Longmuir S, Koistinaho J, Donnelly PS, Crouch PJ, Tammen I, White AR, Kanninen KM., Acta Neuropathol Commun 2(), 2014
PMID: 24581221
Lithium and autophagy.
Motoi Y, Shimada K, Ishiguro K, Hattori N., ACS Chem Neurosci 5(6), 2014
PMID: 24738557
X-ray fluorescence imaging reveals subcellular biometal disturbances in a childhood neurodegenerative disorder.
Grubman A, James SA, James J, Duncan C, Volitakis I, Hickey JL, Crouch PJ, Donnelly PS, Kanninen KM, Liddell JR, Cotman SL, de Jonge, White AR., Chem Sci 5(6), 2014
PMID: 24976945
Induction of lysosomal biogenesis in atherosclerotic macrophages can rescue lipid-induced lysosomal dysfunction and downstream sequelae.
Emanuel R, Sergin I, Bhattacharya S, Turner J, Epelman S, Settembre C, Diwan A, Ballabio A, Razani B., Arterioscler Thromb Vasc Biol 34(9), 2014
PMID: 25060788
Identifying protein partners of CLN8, an ER-resident protein involved in neuronal ceroid lipofuscinosis.
Passantino R, Cascio C, Deidda I, Galizzi G, Russo D, Spedale G, Guarneri P., Biochim Biophys Acta 1833(3), 2013
PMID: 23142642
The endolysosomal system in cell death and survival.
Repnik U, Česen MH, Turk B., Cold Spring Harb Perspect Biol 5(1), 2013
PMID: 23284043
A novel interaction between aging and ER overload in a protein conformational dementia.
Schipanski A, Lange S, Segref A, Gutschmidt A, Lomas DA, Miranda E, Schweizer M, Hoppe T, Glatzel M., Genetics 193(3), 2013
PMID: 23335331
Use of model organisms for the study of neuronal ceroid lipofuscinosis.
Bond M, Holthaus SM, Tammen I, Tear G, Russell C., Biochim Biophys Acta 1832(11), 2013
PMID: 23338040
Altered biometal homeostasis is associated with CLN6 mRNA loss in mouse neuronal ceroid lipofuscinosis.
Kanninen KM, Grubman A, Caragounis A, Duncan C, Parker SJ, Lidgerwood GE, Volitakis I, Ganio G, Crouch PJ, White AR., Biol Open 2(6), 2013
PMID: 23789114
NCL disease mechanisms.
Palmer DN, Barry LA, Tyynelä J, Cooper JD., Biochim Biophys Acta 1832(11), 2013
PMID: 23707513
Conformational defects underlie proteasomal degradation of Dent's disease-causing mutants of ClC-5.
D'Antonio C, Molinski S, Ahmadi S, Huan LJ, Wellhauser L, Bear CE., Biochem J 452(3), 2013
PMID: 23566014
Lysosomal membrane permeability stimulates protein aggregate formation in neurons of a lysosomal disease.
Micsenyi MC, Sikora J, Stephney G, Dobrenis K, Walkley SU., J Neurosci 33(26), 2013
PMID: 23804102
Progressive retinal degeneration and glial activation in the CLN6 (nclf) mouse model of neuronal ceroid lipofuscinosis: a beneficial effect of DHA and curcumin supplementation.
Mirza M, Volz C, Karlstetter M, Langiu M, Somogyi A, Ruonala MO, Tamm ER, Jägle H, Langmann T., PLoS One 8(10), 2013
PMID: 24124525
A murine model of variant late infantile ceroid lipofuscinosis recapitulates behavioral and pathological phenotypes of human disease.
Morgan JP, Magee H, Wong A, Nelson T, Koch B, Cooper JD, Weimer JM., PLoS One 8(11), 2013
PMID: 24223841

50 References

Daten bereitgestellt von Europe PubMed Central.

Accumulation of bis(monoacylglycero)phosphate and gangliosides in mouse models of neuronal ceroid lipofuscinosis.
Jabs S, Quitsch A, Kakela R, Koch B, Tyynela J, Brade H, Glatzel M, Walkley S, Saftig P, Vanier MT, Braulke T., J. Neurochem. 106(3), 2008
PMID: 18498441
Autophagy, mitochondria and cell death in lysosomal storage diseases.
Kiselyov K, Jennigs JJ Jr, Rbaibi Y, Chu CT., Autophagy 3(3), 2007
PMID: 17329960
Autophagy and the ubiquitin-proteasome system: collaborators in neuroprotection.
Nedelsky NB, Todd PK, Taylor JP., Biochim. Biophys. Acta 1782(12), 2008
PMID: 18930136
Monitoring autophagy by electron microscopy in Mammalian cells.
Yla-Anttila P, Vihinen H, Jokitalo E, Eskelinen EL., Meth. Enzymol. 452(), 2009
PMID: 19200881
Neuronal ceroid lipofuscinoses.
Jalanko A, Braulke T., Biochim. Biophys. Acta 1793(4), 2008
PMID: 19084560
No evidence for activation of the unfolded protein response in neuronopathic models of Gaucher disease.
Farfel-Becker T, Vitner E, Dekel H, Leshem N, Enquist IB, Karlsson S, Futerman AH., Hum. Mol. Genet. 18(8), 2009
PMID: 19193629
Pathogenic mutations cause rapid degradation of lysosomal storage disease-related membrane protein CLN6.
Kurze AK, Galliciotti G, Heine C, Mole SE, Quitsch A, Braulke T., Hum. Mutat. 31(2), 2010
PMID: 20020536
Distinct neuropathologic phenotypes after disrupting the chloride transport proteins ClC-6 or ClC-7/Ostm1.
Pressey SN, O'Donnell KJ, Stauber T, Fuhrmann JC, Tyynela J, Jentsch TJ, Cooper JD., J. Neuropathol. Exp. Neurol. 69(12), 2010
PMID: 21107136
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T., EMBO J. 19(21), 2000
PMID: 11060023
The gene mutated in variant late-infantile neuronal ceroid lipofuscinosis (CLN6) and in nclf mutant mice encodes a novel predicted transmembrane protein.
Wheeler RB, Sharp JD, Schultz RA, Joslin JM, Williams RE, Mole SE., Am. J. Hum. Genet. 70(2), 2001
PMID: 11727201
Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse.
Gao H, Boustany RM, Espinola JA, Cotman SL, Srinidhi L, Antonellis KA, Gillis T, Qin X, Liu S, Donahue LR, Bronson RT, Faust JR, Stout D, Haines JL, Lerner TJ, MacDonald ME., Am. J. Hum. Genet. 70(2), 2001
PMID: 11791207
Alpha-Synuclein is degraded by both autophagy and the proteasome.
Webb JL, Ravikumar B, Atkins J, Skepper JN, Rubinsztein DC., J. Biol. Chem. 278(27), 2003
PMID: 12719433
Current state of clinical and morphological features in human NCL.
Goebel HH, Wisniewski KE., Brain Pathol. 14(1), 2004
PMID: 14997938
Selectivity and types of cell death in the neuronal ceroid lipofuscinoses.
Mitchison HM, Lim MJ, Cooper JD., Brain Pathol. 14(1), 2004
PMID: 14997941
Defective endoplasmic reticulum-resident membrane protein CLN6 affects lysosomal degradation of endocytosed arylsulfatase A.
Heine C, Koch B, Storch S, Kohlschutter A, Palmer DN, Braulke T., J. Biol. Chem. 279(21), 2004
PMID: 15010453
CLN6, which is associated with a lysosomal storage disease, is an endoplasmic reticulum protein.
Mole SE, Michaux G, Codlin S, Wheeler RB, Sharp JD, Cutler DF., Exp. Cell Res. 298(2), 2004
PMID: 15265688
Late onset neurodegeneration in the Cln3-/- mouse model of juvenile neuronal ceroid lipofuscinosis is preceded by low level glial activation.
Pontikis CC, Cella CV, Parihar N, Lim MJ, Chakrabarti S, Mitchison HM, Mobley WC, Rezaie P, Pearce DA, Cooper JD., Brain Res. 1023(2), 2004
PMID: 15374749
Human lysosomal acid phosphatase is transported as a transmembrane protein to lysosomes in transfected baby hamster kidney cells.
Waheed A, Gottschalk S, Hille A, Krentler C, Pohlmann R, Braulke T, Hauser H, Geuze H, von Figura K., EMBO J. 7(8), 1988
PMID: 3056714
Neuronal ceroid lipofuscinosis (nclf), a new disorder of the mouse linked to chromosome 9.
Bronson RT, Donahue LR, Johnson KR, Tanner A, Lane PW, Faust JR., Am. J. Med. Genet. 77(4), 1998
PMID: 9600738
Thalamocortical neuron loss and localized astrocytosis in the Cln3Deltaex7/8 knock-in mouse model of Batten disease.
Pontikis CC, Cotman SL, MacDonald ME, Cooper JD., Neurobiol. Dis. 20(3), 2005
PMID: 16006136
Participation of autophagy in storage of lysosomes in neurons from mouse models of neuronal ceroid-lipofuscinoses (Batten disease).
Koike M, Shibata M, Waguri S, Yoshimura K, Tanida I, Kominami E, Gotow T, Peters C, von Figura K, Mizushima N, Saftig P, Uchiyama Y., Am. J. Pathol. 167(6), 2005
PMID: 16314482
Palmitoyl-protein thioesterase-1 deficiency mediates the activation of the unfolded protein response and neuronal apoptosis in INCL.
Zhang Z, Lee YC, Kim SJ, Choi MS, Tsai PC, Xu Y, Xiao YJ, Zhang P, Heffer A, Mukherjee AB., Hum. Mol. Genet. 15(2), 2005
PMID: 16368712
Intracellular inclusions containing mutant alpha1-antitrypsin Z are propagated in the absence of autophagic activity.
Kamimoto T, Shoji S, Hidvegi T, Mizushima N, Umebayashi K, Perlmutter DH, Yoshimori T., J. Biol. Chem. 281(7), 2005
PMID: 16365039
ER stress and neurodegenerative diseases.
Lindholm D, Wootz H, Korhonen L., Cell Death Differ. 13(3), 2006
PMID: 16397584
Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice.
Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, Yokoyama M, Mishima K, Saito I, Okano H, Mizushima N., Nature 441(7095), 2006
PMID: 16625204
Loss of autophagy in the central nervous system causes neurodegeneration in mice.
Komatsu M, Waguri S, Chiba T, Murata S, Iwata J, Tanida I, Ueno T, Koike M, Uchiyama Y, Kominami E, Tanaka K., Nature 441(7095), 2006
PMID: 16625205
Autophagy is disrupted in a knock-in mouse model of juvenile neuronal ceroid lipofuscinosis.
Cao Y, Espinola JA, Fossale E, Massey AC, Cuervo AM, MacDonald ME, Cotman SL., J. Biol. Chem. 281(29), 2006
PMID: 16714284
Progress towards understanding disease mechanisms in small vertebrate models of neuronal ceroid lipofuscinosis.
Cooper JD, Russell C, Mitchison HM., Biochim. Biophys. Acta 1762(10), 2006
PMID: 17023146
Successive neuron loss in the thalamus and cortex in a mouse model of infantile neuronal ceroid lipofuscinosis.
Kielar C, Maddox L, Bible E, Pontikis CC, Macauley SL, Griffey MA, Wong M, Sands MS, Cooper JD., Neurobiol. Dis. 25(1), 2006
PMID: 17046272
Topology and endoplasmic reticulum retention signals of the lysosomal storage disease-related membrane protein CLN6.
Heine C, Quitsch A, Storch S, Martin Y, Lonka L, Lehesjoki AE, Mole SE, Braulke T., Mol. Membr. Biol. 24(1), 2007
PMID: 17453415
Signal integration in the endoplasmic reticulum unfolded protein response.
Ron D, Walter P., Nat. Rev. Mol. Cell Biol. 8(7), 2007
PMID: 17565364
ER chaperones in mammalian development and human diseases.
Ni M, Lee AS., FEBS Lett. 581(19), 2007
PMID: 17481612
p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy.
Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Overvatn A, Bjorkoy G, Johansen T., J. Biol. Chem. 282(33), 2007
PMID: 17580304
A block of autophagy in lysosomal storage disorders.
Settembre C, Fraldi A, Jahreiss L, Spampanato C, Venturi C, Medina D, de Pablo R, Tacchetti C, Rubinsztein DC, Ballabio A., Hum. Mol. Genet. 17(1), 2007
PMID: 17913701
Autophagy in the pathogenesis of disease.
Levine B, Kroemer G., Cell 132(1), 2008
PMID: 18191218
Dissecting the ER-associated degradation of a misfolded polytopic membrane protein.
Nakatsukasa K, Huyer G, Michaelis S, Brodsky JL., Cell 132(1), 2008
PMID: 18191224
Autophagy fights disease through cellular self-digestion.
Mizushima N, Levine B, Cuervo AM, Klionsky DJ., Nature 451(7182), 2008
PMID: 18305538
The neuronal ceroid lipofuscinoses: the same, but different?
Cooper JD., Biochem. Soc. Trans. 38(6), 2010
PMID: 21118105
Cerebellar alterations and gait defects as therapeutic outcome measures for enzyme replacement therapy in α-mannosidosis.
Damme M, Stroobants S, Walkley SU, Lullmann-Rauch R, D'Hooge R, Fogh J, Saftig P, Lubke T, Blanz J., J. Neuropathol. Exp. Neurol. 70(1), 2011
PMID: 21157375
Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6.
Arsov T, Smith KR, Damiano J, Franceschetti S, Canafoglia L, Bromhead CJ, Andermann E, Vears DF, Cossette P, Rajagopalan S, McDougall A, Sofia V, Farrell M, Aguglia U, Zini A, Meletti S, Morbin M, Mullen S, Andermann F, Mole SE, Bahlo M, Berkovic SF., Am. J. Hum. Genet. 88(5), 2011
PMID: 21549341
Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis.
Noskova L, Stranecky V, Hartmannova H, Pristoupilova A, Baresova V, Ivanek R, Hulkova H, Jahnova H, van der Zee J, Staropoli JF, Sims KB, Tyynela J, Van Broeckhoven C, Nijssen PC, Mole SE, Elleder M, Kmoch S., Am. J. Hum. Genet. 89(2), 2011
PMID: 21820099
High expression of disease-related Cln6 in the cerebral cortex, purkinje cells, dentate gyrus, and hippocampal ca1 neurons.
Thelen M, Fehr S, Schweizer M, Braulke T, Galliciotti G., J. Neurosci. Res. 90(3), 2011
PMID: 22012656

Export

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®

Quellen

PMID: 22536393
PubMed | Europe PMC

Suchen in

Google Scholar