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Cited by 252Alzheimer's disease research and treatmentsParkinson's Disease Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration Mechanisms

Protein phosphorylation in neurodegeneration: friend or foe?

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Tenreiro, Sandra, Eckermann, Katrin, Outeiro, Tiago F.·2014·Frontiers in Molecular Neuroscience
DOI 10.3389/fnmol.2014.00042PMC PMC4026737
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Abstract

Protein misfolding and aggregation is a common hallmark in neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and fronto-temporal dementia (FTD). In these disorders, the misfolding and aggregation of specific proteins occurs alongside neuronal degeneration in somewhat specific brain areas, depending on the disorder and the stage of the disease. However, we still do not fully understand the mechanisms governing protein aggregation, and whether this constitutes a protective or detrimental process. In PD, alpha-synuclein (aSyn) forms protein aggregates, known as Lewy bodies, and is phosphorylated at serine 129. Other residues have also been shown to be phosphorylated, but the significance of phosphorylation in the biology and pathophysiology of the protein is still controversial. In AD and in FTD, hyperphosphorylation of tau protein causes its misfolding and aggregation. Again, our understanding of the precise consequences of tau phosphorylation in the biology and pathophysiology of the protein is still limited. Through the use of a variety of model organisms and technical approaches, we are now gaining stronger insight into the effects of phosphorylation in the behavior of these proteins. In this review, we cover recent findings in the field and discuss how targeting phosphorylation events might be used for therapeutic intervention in these devastating diseases of the nervous system.

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  • Compared to unaffected Sst supertypes, vulnerable Sst supertypes collectively downregulated specific kinases and E3 ubiquitin ligases.

    “Compared to unaffected Sst supertypes, the vulnerable Sst supertypes collectively downregulated specific kinases (from the tyrosine kinase56 and calcium2+/calmodulin-dependent kinase57 families) (Fig. 5h, green) and E3 ubiquitin ligases (from the homologous to the E6-AP carboxyl terminus (HECT) family58) (Fig. 5h, blue).”

    From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [56]

    The sections on kinases involved in tau phosphorylation and on α-synuclein cytotoxicity discuss phosphorylation in neurodegeneration, not comparisons between vulnerable and unaffected Sst supertypes. Searches for Sst supertypes, calcium/calmodulin-dependent kinases, and HECT-family E3 ligases found no passage reporting the claimed downregulation. Page numbers were not available in our copy. (LLM, conf=0.74)

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Sorted by citations

Authors
Tenreiro, S., Eckermann, K., & Outeiro, T. F.
Affiliations
  • Instituto de Medicina Molecular João Lobo Antunes (PT)
  • Universitätsmedizin Göttingen (DE)
  • University of Lisbon (PT)
Corresponding author
Outeiro, Tiago F.
ORCID
Venue
Frontiers in Molecular Neuroscience
Publisher
Frontiers Media SA
Published
2014-05-13
Volume
7
Pages
42-42
ISSN
1662-5099 (ISSN-L)
DOI
10.3389/fnmol.2014.00042
PMC
PMC4026737
OpenAlex
W2045489211
Cited by
252
References
33
Citations by year
2026: 9 · 2025: 16 · 2024: 20 · 2023: 22 · 2022: 28 · 2021: 29 · 2020: 18 · 2019: 24 · 2018: 17 · 2017: 17 · 2016: 25 · 2015: 18 · 2014: 8 · 2013: 1
FWCI
2.65
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Molecular Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
  • GRO (submittedVersion, cc-by)
  • Newcastle University ePrints (Newcastle Univesity) (cc-by)
Funders
  • Deutsche Forschungsgemeinschaft
  • Fundação para a Ciência e a Tecnologia (PTDC/SAU-NEU/105215/2008, PTDC/BIA-BCM/117975/2010)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
protein phosphorylation, neurodegeneration, protein misfolding, protein aggregation, Alzheimer's disease, Parkinson's disease, frontotemporal dementia, alpha-synuclein, tau hyperphosphorylation, serine 129 phosphorylation, Lewy bodies

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