ReviewSeminars in cell & developmental biology2022
Targeting tau only extracellularly is likely to be less efficacious than targeting it both intra- and extracellularly.
Review in Seminars in cell & developmental biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 41 citations in OpenAlex.
- PP2A methylesterase, PME-1, and PP2A methyltransferase, LCMT-1, control sensitivity to impairments caused by injury-related oligomeric tau.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Clearing truncated tau protein restores neuronal function and prevents microglia activation in tauopathy mice.Cell reports · 2025Article
- Advances of therapeutic strategies for Alzheimer's disease.Journal of neurology · 2025Review
- Tau-Targeted Therapeutic Strategies: Mechanistic Targets, Clinical Pipelines, and Analysis of Failures.Cells · 2025Review
- AAV-mediated peripheral scFv's administration to reduce cerebral tau in adult P301S transgenic mice: Mono-vs. combination therapy.Molecular therapy. Methods & clinical development · 2025Article
- Axonal tau reduction ameliorates tau and amyloid pathology in a mouse model of Alzheimer's disease.Translational neurodegeneration · 2025Article
- Interplay Between Aging and Tau Pathology in Alzheimer's Disease: Mechanisms and Translational Perspectives.Antioxidants (Basel, Switzerland) · 2025Review
- "Proteinjury": a universal pathological mechanism mediated by cerebrospinal fluid in neurodegeneration and trauma.Frontiers in cell and developmental biology · 2025Review
- Single-domain antibody-based protein degrader for synucleinopathies.Molecular neurodegeneration · 2024Article
- The Enigma of Tau Protein Aggregation: Mechanistic Insights and Future Challenges.International journal of molecular sciences · 2024Review
- Single-Domain Antibody-Based Protein Degrader for Synucleinopathies.bioRxiv : the preprint server for biology · 2024Article
- Tau Immunotherapies for Alzheimer's Disease and Related Tauopathies: Status of Trials and Insights from Preclinical Studies.Journal of Alzheimer's disease : JAD · 2024Review
- 5-HT4 receptor agonists treatment reduces tau pathology and behavioral deficit in the PS19 mouse model of tauopathy.Frontiers in cellular neuroscience · 2024Article
- Tau-targeting therapies for Alzheimer disease: current status and future directions.Nature reviews. Neurology · 2023Review
- Analysis of clinical failure of anti-tau and anti-synuclein antibodies in neurodegeneration using a quantitative systems pharmacology model.Scientific reports · 2023Article
- APP mediates tau uptake and its overexpression leads to the exacerbated tau pathology.Cellular and molecular life sciences : CMLS · 2023Article
- Amyloid-β targeting immunisation in aged non-human primate (Microcebus murinus).Brain, behavior, and immunity · 2023Article
- Development of brain-penetrable antibody radioligands forFrontiers in nuclear medicine · 2023Article
- Tau antibody 77G7 targeting microtubule binding domain suppresses proteopathic tau to seed tau aggregation.CNS neuroscience & therapeutics · 2022Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Aggregation of the tau protein is thought to be responsible for the neurodegeneration and subsequent functional impairments in diseases that are collectively named tauopathies. Alzheimer's disease is the most common tauopathy, but the group consists of over 20 different diseases, many of which have tau pathology as their primary feature. The development of tau therapies has mainly focused on preventing the formation of and/or clearing these aggregates. Of these, immunotherapies that aim to either elicit endogenous tau antibodies or deliver exogenous ones are the most common approach in clinical trials. While their mechanism of action can involve several pathways, both extra- and intracellular, pharmaceutical companies have primarily focused on antibody-mediated clearance of extracellular tau. As we have pointed out over the years, this is rather surprising because it is well known that most of pathological tau protein is found intracellularly. It has been repeatedly shown by several groups over the past decades that antibodies can enter neurons and that their cellular uptake can be enhanced by various means, particularly by altering their charge. Here, we will briefly describe the potential extra- and intracellular mechanisms involved in antibody-mediated clearance of tau pathology, discuss these in the context of recent failures of some of the tau antibody trials, and finally provide a brief overview of how the intracellular efficacy of tau antibodies can potentially be further improved by certain modifications that aim to enhance tau clearance via specific intracellular degradation pathways.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.