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.
Keywords: Tau aggregation, tau oligomers, pathological tau, small molecules, immunotherapy.
Rights & PermissionsPrintExport