Amyloid precursor protein (app) is a membrane protein that has a role in the protection of synaptic integrity



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Amyloid precursor protein (APP) is a membrane protein that has a role in the protection of synaptic integrity (Kang et al., 1987).

  • Amyloid precursor protein (APP) is a membrane protein that has a role in the protection of synaptic integrity (Kang et al., 1987).

  • Aβ is formed as a result of enzymatic breakdown of some peptide components from APP.

  • They convert to highly insoluble and proteolysis-resistant fibrils called senile plaques by accumulation of toxic Aβ42 forms.

  • Accumulation of Aβ42 in brain inhibits LTP.

  • Mutation of APP, PS1 and PS2 genes increases to produce Aβ42 formation (Galiberti and Scapini, 2012).



Notch is a cell surface receptor that, when activated by ligands such as Jagged and Delta, is cleaved at the membrane resulting in the release of «an intracellular domain of Notch» (NICD).

  • Notch is a cell surface receptor that, when activated by ligands such as Jagged and Delta, is cleaved at the membrane resulting in the release of «an intracellular domain of Notch» (NICD).

  • NICD then translocate to the nucleus where it regulates the transcription of various genes.

  • γ-secretase-mediated Notch signaling plays an essential role in the regulation of cell fate during development of many organ systems including the brain as indicated by embryonic lethality and defective neurogenesis that is identical in Notch and PS1-deficient mice (Shen et al., 1997)

  • Mutations of PS1 and PS2 also disrupt constructive interaction and signaling in Notch pathway and increases diathesis to produce Aβ42 formation (Steiner et al., 2001).







ApoE is one of the key lipoproteins of lipoprotein complexes that regulate the metabolism of lipids.

  • ApoE is one of the key lipoproteins of lipoprotein complexes that regulate the metabolism of lipids.

  • Three common polymorphisms in the APOE gene, ε2, ε3, and ε4, result in single amino acid changes in the ApoE protein.





Indeed, AD is defined as a pathological remodelling characterized by memory failures, retardation of cognitive functions, and accompanying behavioral defects that appear due to an unreliable neurotransmission between hippocampus or other related limbic system formations, and entorhinal and associative cortex because of neuronal loses of these areas.

  • Indeed, AD is defined as a pathological remodelling characterized by memory failures, retardation of cognitive functions, and accompanying behavioral defects that appear due to an unreliable neurotransmission between hippocampus or other related limbic system formations, and entorhinal and associative cortex because of neuronal loses of these areas.

  • The process is directly associated to senile plaques by accumulation of toxic Aβ42 and NFTs depending on excessive phosphorylation of tau.



Dendritic and axonal alterations (especially in septo-hippocampal pathway)

  • Dendritic and axonal alterations (especially in septo-hippocampal pathway)

  • Neuronal losses (apoptosis) (especially in hippocampus, entorinal and associative regions cortex)

      • Activation of synaptic caspase
      • Damage in the ectopic cell cycle proteins such as proliferating cell (neuron) nuclear antigen (PCNA) making repair in DNA (it causes to produce Aβ)
  • Synaptic losses in septohippocampal pathway





















How can the better animal models be developed for Alzheimer studies?

  • How can the better animal models be developed for Alzheimer studies?

  • Could other neurotransmitter systems such as DA, NO, agmatin and other polyamines be new targets in development of new drugs and treatment of AD?

  • Could etiopatogenezis of AD be related to neurodevelopmental processes like in autism and schizophrenia?

  • How can we develop to our research strategies straight radical treatments?



We have no drug that provide a radical treatment in AD.

  • We have no drug that provide a radical treatment in AD.

  • New trend in pharmacotherapy may be based on reversing the negative neuroplasticity.

  • The agents that both inhibit neurodegeneration and stimulate regeneration may present more radical solutions via reversing the adverse neuroplasticity.



Üsküdar University supported to accommodation and travel for the meeting.

  • Üsküdar University supported to accommodation and travel for the meeting.

  • Thanks for Mrs. Dilara Gürgüç for her valuable assistance on the presentation.




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