Neuroprotective effects of Cerebrolysin in triple repeat Tau transgenic model of Pick's disease and fronto-temporal tauopathies.

Abstract

BACKGROUND:

Tauopathies are a group of neurodegenerative disorders with accumulation of three-repeat (3R) or four-repeat (4R) Tau. While 3R tau is found in Pick's disease and Alzheimer's disease (AD), 4R tau is more abundant in corticobasal degeneration, progressive supranuclear palsy, and AD. We have previously shown that Cerebrolysin™ (CBL), a neuropeptide mixture with neurotrophic effects, ameliorates the pathology in amyloid precursor protein transgenic (tg) mouse model of AD and 4R tau, however it is unclear if CBL ameliorates the deficits and neuropathology in the mouse model of Pick's disease over expressing 3R tau.

RESULTS:

Mice expressing 3R tau (L266V and G272V mutations) under the mThy-1 promoter were treated with CBL in two separate groups, the first was 3 months old (treated for 3 months, IP) and the second was 6 months old (treated for 3 months, IP) at the start of the treatment. We found that although the levels of total 3R tau were unchanged, CBL reduced the levels of hyper-phosphorylated tau in both groups of mice. This was accompanied by reduced neurodegenerative pathology in the neocortex and hippocampus in both groups and by improvements in the behavioral deficits in the nest-building test and water maze in the 3-6 month group.

CONCLUSION:

Taken together these results support the notion that CBL may be beneficial in other taupathy models by reducing the levels of aberrantly phosphorylated tau.

• Authors: Edward Rockenstein, Kiren Ubhi, Michael Mante, Jazmin Florio, Anthony Adame, Stefan Winter, Hemma Brandstaetter, Dieter Meier, Eliezer Masliah
• Journal: BMC neuroscience (BMC Neurosci) Vol. 16 Pg. 85 (Nov 26 2015) ISSN: 1471-2202 [Electronic] England
• PMID: 26611895 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acids
• MAPT protein, human
• Neuroprotective Agents
• tau Proteins
• cerebrolysin
• Glycogen Synthase Kinase 3 beta
• Proto-Oncogene Proteins c-akt
• Glycogen Synthase Kinase 3

Topics

• Aging (drug effects, metabolism, pathology)
• Amino Acids (pharmacology)
• Animals
• Cerebral Cortex (drug effects, metabolism, pathology)
• Disease Models, Animal
• Glycogen Synthase Kinase 3 (metabolism)
• Glycogen Synthase Kinase 3 beta
• Hippocampus (drug effects, metabolism, pathology)
• Humans
• Mice, Inbred C57BL
• Mice, Transgenic
• Mutation
• Neuroprotective Agents (pharmacology)
• Phosphorylation (drug effects)
• Pick Disease of the Brain (drug therapy, metabolism, pathology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Tauopathies (drug therapy, metabolism, pathology)
• tau Proteins (genetics, metabolism)