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Interplay between Aβ, Ceramides and Hyperphosphorylated Tau in Alzheimer’s Disease (CROSBI ID 54445)

Prilog u knjizi | izvorni znanstveni rad

Jazvinšćak Jembrek, Maja ; Babić, Mirjana ; Pivac, Nela ; Šimić, Goran Interplay between Aβ, Ceramides and Hyperphosphorylated Tau in Alzheimer’s Disease // Sphingomyelin and Ceramides: Occurrence, Biosynthesis and Role in Disease / Watkins, Cecilia L. (ur.). New York (NY): Nova Science Publishers, 2015. str. 53-84

Podaci o odgovornosti

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

engleski

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

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.

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

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Podaci o prilogu

53-84.

objavljeno

Podaci o knjizi

Sphingomyelin and Ceramides: Occurrence, Biosynthesis and Role in Disease

Watkins, Cecilia L.

New York (NY): Nova Science Publishers

2015.

978-1-63482-553-5

Povezanost rada

Temeljne medicinske znanosti