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Cited by 230Lysosomal Storage Disorders ResearchGlycogen Storage Diseases and MyoclonusAutophagy in Disease and Therapy

The rapidly evolving view of lysosomal storage diseases

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Parenti, Giancarlo, Medina, Diego L, Ballabio, Andrea·2021·EMBO Molecular Medicine
DOI 10.15252/emmm.202012836PMC PMC7863408
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Abstract

Lysosomal storage diseases are a group of metabolic disorders caused by deficiencies of several components of lysosomal function. Most commonly affected are lysosomal hydrolases, which are involved in the breakdown and recycling of a variety of complex molecules and cellular structures. The understanding of lysosomal biology has progressively improved over time. Lysosomes are no longer viewed as organelles exclusively involved in catabolic pathways, but rather as highly dynamic elements of the autophagic‐lysosomal pathway, involved in multiple cellular functions, including signaling, and able to adapt to environmental stimuli. This refined vision of lysosomes has substantially impacted on our understanding of the pathophysiology of lysosomal disorders. It is now clear that substrate accumulation triggers complex pathogenetic cascades that are responsible for disease pathology, such as aberrant vesicle trafficking, impairment of autophagy, dysregulation of signaling pathways, abnormalities of calcium homeostasis, and mitochondrial dysfunction. Novel technologies, in most cases based on high‐throughput approaches, have significantly contributed to the characterization of lysosomal biology or lysosomal dysfunction and have the potential to facilitate diagnostic processes, and to enable the identification of new therapeutic targets.

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  • Cathepsin D knockout mice accumulate Ab in addition to lipofuscin.

    “As an example, cathepsin D knockout mice accumulate Ab in addition to lipofuscin, and Alzheimer’s pathology has been observed in postmortem tissues from several NCL patients.125–127”

    From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [126]

    The Secondary storage section (page unavailable) reports amyloid-β accumulation in lysosomal storage diseases generally. It does not say that cathepsin D knockout mice accumulate amyloid-β or lipofuscin; searches for cathepsin D and lipofuscin found no passage establishing that specific finding. (LLM, conf=0.79)

    Experimental — accuracy not yet measured

  • Alzheimer's pathology has been observed in postmortem tissues from several NCL patients.

    “As an example, cathepsin D knockout mice accumulate Ab in addition to lipofuscin, and Alzheimer’s pathology has been observed in postmortem tissues from several NCL patients.125–127”

    From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [126]

    The Secondary storage section links lysosomal storage diseases broadly to proteins associated with Alzheimer’s disease, but does not report Alzheimer’s pathology in postmortem tissue from NCL patients. Searches for postmortem NCL tissue and Alzheimer’s pathology found no passage addressing that observation in our copy. (LLM, conf=0.73)

    Experimental — accuracy not yet measured

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Authors
Parenti, G., Medina, D. L., & Ballabio, A.
Affiliations
  • Federico II University Hospital (IT)
  • Baylor College of Medicine (US)
Corresponding author
Ballabio, Andrea
ORCID
Venue
EMBO Molecular Medicine
Publisher
Springer Science and Business Media LLC
Published
2021-01-18
Volume
13
Issue
2
Pages
e12836-e12836
ISSN
  • 1757-4676 (ISSN-L)
  • 1757-4684
DOI
10.15252/emmm.202012836
PMC
PMC7863408
OpenAlex
W3124638407
Cited by
230
References
13
Citations by year
2026: 28 · 2025: 48 · 2024: 44 · 2023: 40 · 2022: 48 · 2021: 21 · 2020: 1
FWCI
5.13
Type
journal article
Language
en
Open access
Licence
Locations
  • EMBO Molecular Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Fondazione Telethon (TGM16CB6)
  • H2020 European Research Council (694282)
  • National Institutes of Health (R01‐NS078072)
  • Associazione Italiana per la Ricerca sul Cancro
  • Associazione Italiana Rett
Topics
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
  • Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
lysosomal storage disease, lysosomes, lysosomal enzymes, autophagy, substrate accumulation, vesicle trafficking, calcium homeostasis, mitochondrial dysfunction, signaling pathways, high-throughput screening, diagnostic technologies, therapeutic target
MeSH terms
Autophagy, Humans, Lysosomes, Metabolic Diseases, Lysosomal Storage Diseases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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