<scp>ER</scp>‐phagy in neurodegeneration

Hill, Melissa A.; Sykes, Alex M.; Mellick, George D.

doi:10.1002/jnr.25225

Cited by 9 publications

(3 citation statements)

References 142 publications

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“…Among interactions of a group of proteins not mapped by the aforementioned pathway analysis in the TF-HaloMS dataset ( P > .001, Supplementary Fig. S4 and Supplementary Table S16 ), we found a novel subnetwork of proteins involved in ER-phagy, neurodegenerative disease [ 93 ], ER-phagy, neurodegenerative disease, and myelodysplastic and master regulators in adipocytes ( Supplementary Fig. S10D and Supplementary Table S33 ).…”

Section: Resultsmentioning

confidence: 99%

Mapping adipocyte interactome networks by HaloTag-enrichment-mass spectrometry

Yazaki,

Yamanashi,

Nemoto

et al. 2024

Biology Methods and Protocols

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Mapping protein interaction complexes in their natural state in vivo is arguably the Holy Grail of protein network analysis. Detection of protein interaction stoichiometry has been an important technical challenge, as few studies have focused on this. This may however be solved by artificial intelligence and proteomics. Here, we describe the development of HaloMS, a high-throughput HaloTag-based affinity purification–mass spectrometry assay for protein interaction discovery. The approach enables the rapid capture of newly expressed proteins, eliminating tedious conventional one-by-one assays. As a proof-of-principle, we used HaloMS to evaluate the protein complex interactions of 17 regulatory proteins in human adipocytes. The adipocyte interactome network was validated using an in vitro pull-down assay and artificial intelligence-based prediction tools. Applying HaloMS to probe adipocyte differentiation facilitated the identification of previously unknown transcription factor–protein complexes, revealing proteome-wide human adipocyte transcription factor networks and shedding light on how different pathways are integrated.

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Section: Resultsmentioning

confidence: 99%

Mapping adipocyte interactome networks by HaloTag-enrichment-mass spectrometry

Yazaki,

Yamanashi,

Nemoto

et al. 2024

Biology Methods and Protocols

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“…Disorders of ER structure and function have also been identified in AD, PD, and prion diseases. On top of this, abnormalities of ER-phagy or RE degradation by lysosomes have been observed in AD, PD, Niemann–Pick type C, and schizophrenia [ 12 , 53 ]. Gupta and his team also identified large changes in the expression of genes encoding nuclear transcription factors by analyzing data from 300,000 patients with 30 different diseases of aging [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Cellular Organelle-Related Transcriptomic Profile Abnormalities in Neuronopathic Types of Mucopolysaccharidosis: A Comparison with Other Neurodegenerative Diseases

Wiśniewska,

Gaffke,

Żabińska

et al. 2024

CIMB

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Mucopolysaccharidoses (MPS) are a group of diseases caused by mutations in genes encoding lysosomal enzymes that catalyze reactions of glycosaminoglycan (GAG) degradation. As a result, GAGs accumulate in lysosomes, impairing the proper functioning of entire cells and tissues. There are 14 types/subtypes of MPS, which are differentiated by the kind(s) of accumulated GAG(s) and the type of a non-functional lysosomal enzyme. Some of these types (severe forms of MPS types I and II, MPS III, and MPS VII) are characterized by extensive central nervous system disorders. The aim of this work was to identify, using transcriptomic methods, organelle-related genes whose expression levels are changed in neuronopathic types of MPS compared to healthy cells while remaining unchanged in non-neuronopathic types of MPS. The study was conducted with fibroblast lines derived from patients with neuronopathic and non-neuronopathic types of MPS and control (healthy) fibroblasts. Transcriptomic analysis has identified genes related to cellular organelles whose expression is altered. Then, using fluorescence and electron microscopy, we assessed the morphology of selected structures. Our analyses indicated that the genes whose expression is affected in neuronopathic MPS are often associated with the structures or functions of the cell nucleus, endoplasmic reticulum, or Golgi apparatus. Electron microscopic studies confirmed disruptions in the structures of these organelles. Special attention was paid to up-regulated genes, such as PDIA3 and MFGE8, and down-regulated genes, such as ARL6IP6, ABHD5, PDE4DIP, YIPF5, and CLDN11. Of particular interest is also the GM130 (GOLGA2) gene, which encodes golgin A2, which revealed an increased expression in neuronopathic MPS types. We propose to consider the levels of mRNAs of these genes as candidates for biomarkers of neurodegeneration in MPS. These genes may also become potential targets for therapies under development for neurological disorders associated with MPS and candidates for markers of the effectiveness of these therapies. Although fibroblasts rather than nerve cells were used in this study, it is worth noting that potential genetic markers characteristic solely of neurons would be impractical in testing patients, contrary to somatic cells that can be relatively easily obtained from assessed persons.

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“…Neurons are particularly susceptible to accumulating unwanted cellular products, so proper regulation of the autophagy process is crucial. Indeed, it has been reported that alterations in autophagy may be associated with neurodegenerative diseases such as Alzheimer's, Parkinson's, and NPC [53]. As already known, the liver and CNS are among the organs most affected by NPC diseases.…”

Section: Autophagy In Npcmentioning

confidence: 96%

Alterations in Proteostasis Mechanisms in Niemann–Pick Type C Disease

Servín Muñoz,

Ortuño-Sahagún,

Griñán-Ferré

et al. 2024

IJMS

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Niemann–Pick Type C (NPC) represents an autosomal recessive disorder with an incidence rate of 1 in 150,000 live births, classified within lysosomal storage diseases (LSDs). The abnormal accumulation of unesterified cholesterol characterizes the pathophysiology of NPC. This phenomenon is not unique to NPC, as analogous accumulations have also been observed in Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative disorders. Interestingly, disturbances in the folding of the mutant protein NPC1 I1061T are accompanied by the aggregation of proteins such as hyperphosphorylated tau, α-synuclein, TDP-43, and β-amyloid peptide. These accumulations suggest potential disruptions in proteostasis, a regulatory process encompassing four principal mechanisms: synthesis, folding, maintenance of folding, and protein degradation. The dysregulation of these processes leads to excessive accumulation of abnormal proteins that impair cell function and trigger cytotoxicity. This comprehensive review delineates reported alterations across proteostasis mechanisms in NPC, encompassing changes in processes from synthesis to degradation. Additionally, it discusses therapeutic interventions targeting pharmacological facets of proteostasis in NPC. Noteworthy among these interventions is valproic acid, a histone deacetylase inhibitor (HDACi) that modulates acetylation during NPC1 synthesis. In addition, various therapeutic options addressing protein folding modulation, such as abiraterone acetate, DHBP, calnexin, and arimoclomol, are examined. Additionally, treatments impeding NPC1 degradation, exemplified by bortezomib and MG132, are explored as potential strategies. This review consolidates current knowledge on proteostasis dysregulation in NPC and underscores the therapeutic landscape targeting diverse facets of this intricate process.

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ER‐phagy in neurodegeneration

Cited by 9 publications

References 142 publications

Mapping adipocyte interactome networks by HaloTag-enrichment-mass spectrometry

Mapping adipocyte interactome networks by HaloTag-enrichment-mass spectrometry

Cellular Organelle-Related Transcriptomic Profile Abnormalities in Neuronopathic Types of Mucopolysaccharidosis: A Comparison with Other Neurodegenerative Diseases

Alterations in Proteostasis Mechanisms in Niemann–Pick Type C Disease

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