Intra-maxillary Molecular Releasing and its Application in the Assistance of Neurodegenerative Disease Therapeutics SciDoc Publishers | Open Access | Science Journals | Media Partners

The above pathological findings may plot the characteristics of AD. Furthermore in the molecular level, NFT may have neural toxicity by reducing microtubule stability due to tau protein mutation, hyperphosphorylation, and aggregations [38, 39]. The human tau gene locates on chromosome 17 with 16 exons and produces six isoforms by different ways of splicing within two inserts closed to the N-terminus, and three to four highly conserved, imperfect repeat sequences microtubule-binding domains in the C-terminus [40, 41]. Such splicing produces two groups of tau isoforms including three (3R) or four (4R) microtubule-binding repeats. In normal human brain, the 3R:4R tau ratio is around 1:1, while it may increase during neurodegenerative tauopathies [42]. There are two major mutations that will result in tau aggregations into NFTs including intronic and coding mutations [43, 44]. Besides, tau phosphorylation is important in its microtubule-binding process, and insoluble, highly phosphorylated tau may arouse tauopathy and leads to neuronal loss [45]. That implies inhibition of protein kinases by targeting tau phosphorylation process may provide the therapeutic approach to reduce tau aggregations [46]. Current therapeutics of AD is mainly for progression decelerated. Acetylcholinesterase (AChE) inhibitors may provide cognitive enhancement. Donepezil, galantamine and rivastigmine may enhance cholinergic neurotransmission for mild-to-moderate AD [47, 48], while N-methyl-D-aspartate (NMDA) receptor antagonist memantine is recommended for moderate-to-severe AD [49, 50]