Naslov
Interplay between Aβ, Ceramides and Hyperphosphorylated Tau in Alzheimer’s Disease

Autori
Jazvinšćak Jembrek, Maja ; Babić, Mirjana ; Pivac, Nela ; Šimić, Goran

Vrsta, podvrsta i kategorija rada
Poglavlja u knjigama, pregledni

Knjiga
Sphingomyelin and Ceramides: Occurrence, Biosynthesis and Role in Disease

Urednik/ci
Watkins, Cecilia L.

Izdavač
Nova Science Publishers

Grad
New York (NY)

Godina
2015

Raspon stranica
53-84

ISBN
978-1-63482-553-5

Ključne riječi
Ceramides, Aβ, Phospho-tau, Alzheimer's disease

Sažetak
Alzheimer's disease (AD), the most common leading form of dementia in elderly people, is a chronic and progressive neurodegenerative disorder. The most frequently investigated neuropathological hallmarks of AD are extracellular deposits of neurotoxic amyloid β peptide (Aβ) and intracellular aggregates of hyperphosphorylated tau protein. Ceramides, the major molecules of sphingolipid metabolism, have been linked to AD susceptibility and pathogenesis, including both Aβ pathology and tau aggregation. Elevated levels of ceramides directly increase Aβ levels acting on β- secretase, a key enzyme in the proteolytic cleavage of Aβ precursor protein (APP). In turn, soluble and fibrillar forms of Aβ activate sphingomyelinases, enzymes that catalyze the breakdown of sphingomyelin to ceramides, and lead to further increase in Aβ generation. Ceramides are also linked to tau phosphorylation, in particular by modulating activity of protein phosphatase 2A, the major tau phosphatase in the human brain. Hence, preservation of neuronal ceramide homeostasis is of major importance for normal brain functioning. This chapter summarizes recent findings and potential targets for novel therapeutic approaches in AD regarding described devastating Aβ-ceramides-tau cascade.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA