Therapeutic approaches targeting pathological tau aggregates

Julia Gerson, Rakez Kayed

Research output: Contribution to journalReview article

6 Citations (Scopus)

Abstract

Neurodegenerative diseases characterized by the accumulation of tau aggregates are increasing in prevalence to epidemic-like levels and there is currently no effective treatment. For many years, the focus of tau-based research was on the fibrillar, neurofibrillary tangles. However, the compilation of evidence obtained from numerous laboratories in the past few years suggests that soluble intermediate aggregates—tau oligomers—are actually the most toxic protein species in disease. Thus, therapeutic agents that target oligomeric tau specifically may be the most effective routes for treatment. A great deal of progress has been made in the pre-clinical evaluation of a number of different anti-tau therapeutics. Upstream modulators of tau modifications have been evaluated and may provide some benefits, but likely will not be capable of eliminating toxic tau entirely. Protein chaperones capable of modulating the structure of tau and targeting it for degradation are another field of study, however, the broad effects of chaperones make side effects a concern. Thus, more specific agents capable of eliminating the most toxic species in disease are promising. Small molecules designed to inhibit aggregation, as well as immunotherapy with antibodies specific for toxic tau aggregates present the most advancement as potential treatments. The concerted effort across a number of groups to investigate potential mechanisms to inhibit tau toxicity represents great progress in the field and provides hope that effective treatments will be discovered.

Original languageEnglish (US)
Pages (from-to)4028-4039
Number of pages12
JournalCurrent Pharmaceutical Design
Volume22
Issue number26
DOIs
StatePublished - Jul 1 2016

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Poisons
Therapeutics
Neurofibrillary Tangles
Neurodegenerative Diseases
Immunotherapy
Proteins
Antibodies
Research

Keywords

  • Immunotherapy
  • Pathological tau
  • Small molecules
  • Tau aggregation
  • Tau oligomers

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

Therapeutic approaches targeting pathological tau aggregates. / Gerson, Julia; Kayed, Rakez.

In: Current Pharmaceutical Design, Vol. 22, No. 26, 01.07.2016, p. 4028-4039.

Research output: Contribution to journalReview article

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