Unbiased Cell-based Screening in a Neuronal Cell Model of Batten Disease Highlights an Interaction between Ca2+ Homeostasis, Autophagy, and CLN3 Protein Function

Chandrachud, Uma; Walker, Mathew; Simas, Alexandra M.; Heetveld, Sasja; Petcherski, Anton; Klein, Madeleine C; Oh, Hyejin; Wolf, Pavlina; Zhao, Wen-Ning; Norton, Stephanie; Haggarty, Stephen J.; Lloyd-Evans, Emyr; Cotman, Susan L.

doi:10.1074/jbc.m114.621706

Cited by 78 publications

(79 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1683 CLN3 (ceroid-lipofuscinosis, neuronal 3): An endosomal/ lysosomal protein whose deficiency causes inefficient autolysosome clearance and accumulation of autofluorescent lysosomal storage material and ATP5G/subunit c (ATP synthase, H+ transporting, mitochondrial Fo complex, subunit C [subunit 9]). 1684,1685 In human, recessive CLN3 mutations cause juvenile neuronal ceroid lipofuscinosis (JNCL; Batten disease). Recessive CLN3 mutations have also been reported in cases of autophagic vacuolar myopathy and non-syndromic retinal disease.…”

Section: Caspases (Cysteine-dependent Aspartate-directed Proteases)mentioning

confidence: 99%

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Klionsky¹,

Abdelmohsen²,

Abe³

et al. 2016

View full text Add to dashboard Cite

show abstract

Section: Caspases (Cysteine-dependent Aspartate-directed Proteases)mentioning

confidence: 99%

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Klionsky¹,

Abdelmohsen²,

Abe³

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Despite all of this, the function of CLN3 protein remains elusive. The authors hope that the historical research findings presented here will contribute to determining the function of the CLN3 protein and exactly why, CLN3 gene defects adversely affect endosomal‐lysosomal homeostasis, proteome, lipidome, trafficking, maturation, and recycling activities (anHaack et al, ; Appu et al, ; Burkovetskaya et al, ; Cao et al, ; Chandrachud et al, ; Codlin et al, ; Codlin & Mole, ; Gachet et al, ; Golabek et al, ; Holopainen, Saarikoski, Kinnunen, & Jarvela, ; Fossale et al, ; Kama et al, ; Luiro et al, ; Metcalf, Calvi, Seaman, Mitchison, & Cutler, ; Schmidtke et al, ; Stein et al, ; Tecedor et al, ; Vidal‐Donet, Cárcel‐Trullols, Casanova, Aguado, & Knecht, ). Why does CLN3 protein deficiency impact protein palmitoylation?…”

Section: Resultsmentioning

confidence: 96%

The CLN3 gene and protein: What we know

Mirza¹,

Vainshtein

DiRonza

et al. 2019

Molec Gen & Gen Med

Self Cite

View full text Add to dashboard Cite

Background One of the most important steps taken by Beyond Batten Disease Foundation in our quest to cure juvenile Batten (CLN3) disease is to understand the State of the Science. We believe that a strong understanding of where we are in our experimental understanding of the CLN3 gene, its regulation, gene product, protein structure, tissue distribution, biomarker use, and pathological responses to its deficiency, lays the groundwork for determining therapeutic action plans. Objectives To present an unbiased comprehensive reference tool of the experimental understanding of the CLN3 gene and gene product of the same name. Methods BBDF compiled all of the available CLN3 gene and protein data from biological databases, repositories of federally and privately funded projects, patent and trademark offices, science and technology journals, industrial drug and pipeline reports as well as clinical trial reports and with painstaking precision, validated the information together with experts in Batten disease, lysosomal storage disease, lysosome/endosome biology. Results The finished product is an indexed review of the CLN3 gene and protein which is not limited in page size or number of references, references all available primary experiments, and does not draw conclusions for the reader. Conclusions Revisiting the experimental history of a target gene and its product ensures that inaccuracies and contradictions come to light, long‐held beliefs and assumptions continue to be challenged, and information that was previously deemed inconsequential gets a second look. Compiling the information into one manuscript with all appropriate primary references provides quick clues to which studies have been completed under which conditions and what information has been reported. This compendium does not seek to replace original articles or subtopic reviews but provides an historical roadmap to completed works.

show abstract

“…In addition, perturbed mitochondrial Ca 2+ homeostasis has also been observed in the aforementioned LSDs, including decreased Ca 2+ buffering capacity and reduced ATP production as well as mitochondrial fragmentation (Kiselyov et al, 2007, de Pablo-Latorre et al, 2012, Chandrachud et al, 2015). A reduction in mitochondrial membrane potential and concomitant decrease in ATP was shown in a mouse model of NPC1 (Yu et al, 2005).…”

Section: Neurodegeneration In Lsdsmentioning

confidence: 99%

Astrocytes and lysosomal storage diseases

Rao

Kielian²

2016

Neuroscience

View full text Add to dashboard Cite

Lysosomal storage diseases (LSDs) encompass a wide range of disorders characterized by inborn errors of lysosomal function. The majority of LSDs result from genetic defects in lysosomal enzymes, although some arise from mutations in lysosomal proteins that lack known enzymatic activity. Neuropathological abnormalities are a feature of several LSDs and when severe, represent an important determinant in disease outcome. Glial dysfunction, particularly in astrocytes, is also observed in numerous LSDs and has been suggested to impact neurodegeneration. This review will discuss the potential role of astrocytes in LSDs and highlight the possibility of targeting glia as a beneficial strategy to counteract the neuropathology associated with LSDs.

show abstract

Unbiased Cell-based Screening in a Neuronal Cell Model of Batten Disease Highlights an Interaction between Ca2+ Homeostasis, Autophagy, and CLN3 Protein Function

Cited by 78 publications

References 61 publications

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

The CLN3 gene and protein: What we know

Astrocytes and lysosomal storage diseases

Contact Info

Product

Resources

About