Taupathy Therapy Approach

 

Taupathy Therapy Approach

 

The formation of tau aggregates and neurofibrillary tangles (NFTs) are pathological hallmark of diseases termed tauopathies. Tauopathies include the two most common neurodegenerative diseases, Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). However, studies demonstrated that neuron cell death occurs prior to NFT formation in AD (1), indicating that NFTs may not the pathogenic species accountable for the progression of the disease. In rTg4510 mice there was in some brain regions loss of neurons before neurofibrillary lesions appeared, and neurofibrillary pathology appeared with almost no cell loss in other brain regions (2). Moreover, de Calignon found in the rTg4510 mouse model indications that NFTs may even possess protective properties (3).

 

Latest evidence points to the tau oligomers as the toxic species. Tau oligomers are soluble intermediates between tau monomers and NFTs. In a rodent model neuronal cell loss and behavioral deficiencies could be inhibited by reducing tau expression and that without reduction of the number or continued accumulation of NFTs (2). Another study identified tau oligomers appearance as correlated with cognitive impairments in rTg4510 mice (4). Further support that the tau oligomers could be central to neurodegeneration arises from the observation that intracerebral injection even in wild-type mice provokes memory impairments and synaptic dysfunction (5).

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1.Haroutunian V, Davies P, Vianna C, Buxbaum JD, Purohit DP. Tau protein abnormalities asso- ciated with the progression of Alzheimer disease type dementia. Neurobiol Aging (2007) 28:1–7. doi:10.1016/j.neurobiolaging.2005. 11.001

2.Spires TL, Orne JD, Santacruz K, Pitstick R, Carlson GA, Ashe KH, et al. Region-specific dissociation of neuronal loss and neurofibrillary pathology in a mouse model of tauopa- thy. Am J Pathol (2006) 168: 1598–607. doi:10.2353/ajpath. 2006.050840

3.de Calignon A, Fox LM, Pitstick R, Carlson GA, Bacskai BJ, Spires- Jones TL, et al. Caspase activa- tion precedes and leads to tan- gles. Nature (2010) 464:1201–4. doi:10.1038/nature08890

4.Sahara N, Deture M, Ren Y, Ebrahim AS, Kang D, Knight J, et al. Characteristics of TBS- extractable hyperphosphorylated tau species: aggregation interme- diates in rTg4510 mouse brain. J Alzheimers Dis (2013) 33: 249–63.

5.Lasagna-Reeves CA, Castillo- Carranza DL, Sengupta U, Clos AL, Jackson GR, Kayed R. Tau oligomers impair memory and induce synaptic and mito- chondrial dysfunction in wild- type mice. Mol Neurodegener (2011) 6:39. doi:10.1186/1750- 1326-6-39

 

music of animation by: Drops of H2O ( The Filtered Water Treatment ) by J.Lang (c) 2012 Licensed under a Creative Commons Attribution (3.0) license. http://dig.ccmixter.org/files/djlang59/37792 Ft: Airtone