Abstract
Alzheimer’s disease (AD) is the most widespread form of dementia, characterized by memory loss and reduction of cognitive functions that strongly interfere with normal daily life. Numerous evidences show that aggregates of the amyloid beta peptide, formed by 39 to 42 amino acid residues (Aβ39–43), from soluble small oligomers to large fibrils are characteristic markers of this pathology. However, AD is a complex disease and its neurodegenerative molecular mechanism is not yet fully understood. Growing evidence suggests a link between Aβ polymorphic nature, oligomers and fibrils, and specific mechanisms of neurodegeneration. The Aβ variable nature and its multiplicity of interactions with different proteins and organelles reflect the complexity of this pathology. In this review, we analyze the effects of the interaction between Aβ peptide and different cellular compartments in relation to the different kinds and sizes of amyloid aggregates. In particular, Aβ interaction with different cell structures such as the plasma membrane, mitochondria, lysosomes, nucleus, and endoplasmic reticulum is discussed. Further, we analyze the Aβ peptide ability to modify the structure and function of the target organelle, inducing alteration of its physiological role thus contributing to the pathological event. Dysfunction of cellular components terminating with the activation of the cellular death mechanism and subsequent neurodegeneration is also taken into consideration.
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Picone, P., Nuzzo, D., Giacomazza, D. et al. β-Amyloid Peptide: the Cell Compartment Multi-faceted Interaction in Alzheimer’s Disease. Neurotox Res 37, 250–263 (2020). https://doi.org/10.1007/s12640-019-00116-9
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DOI: https://doi.org/10.1007/s12640-019-00116-9