The dark sides of amyloid in Alzheimer's disease pathogenesis.
Although widely explored, the pathogenesis of Alzheimer's disease (AD) has yet to be cleared. Over the past twenty years the so call amyloid cascade hypothesis represented the main research paradigm in AD pathogenesis. In spite of its large consensus, the proposed role of β-amyloid (Aβ) remain to be elucidated. Many evidences are starting to cast doubt on Aβ as the primary causative factor in AD. For instance, Aβ is deposited in the brain following many different kinds of injury. Also, concentration of Aβ needed to induce toxicity in vitro are never reached in vivo. In this review we propose an amyloid-independent interpretation of several AD pathogenic features, such as synaptic plasticity, endo-lysosomal trafficking, cell cycle regulation and neuronal survival.
Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Università degli Studi di Napoli Federico II, Naples, Italy.
Pierpaolo
P
Sorrentino
Dipartimento di Scienze Motorie e del Benessere, Università degli Studi di Napoli Parthenope, Naples, Italy; Istituto di Diagnosi e Cura Hermitage Capodimonte, Naples, Italy.
Antonietta
A
Iuliano
Dipartimento di Scienze Motorie e del Benessere, Università degli Studi di Napoli Parthenope, Naples, Italy; Istituto di Diagnosi e Cura Hermitage Capodimonte, Naples, Italy.
Arianna
A
Polverino
Dipartimento di Scienze Motorie e del Benessere, Università degli Studi di Napoli Parthenope, Naples, Italy; Istituto di Diagnosi e Cura Hermitage Capodimonte, Naples, Italy.
Francesca
F
Jacini
Dipartimento di Scienze Motorie e del Benessere, Università degli Studi di Napoli Parthenope, Naples, Italy; Istituto di Diagnosi e Cura Hermitage Capodimonte, Naples, Italy. Electronic address: giuseppe.sorrentino@uniparthenope.it.
Giuseppe
G
Sorrentino
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000682:Amyloid / Q000502:physiology*; D000818:Animals; D002470:Cell Survival; D006801:Humans; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology; D053763:Presenilins / Q000378:metabolism; D021381:Protein Transport; D012307:Risk Factors; D013569:Synapses / Q000502:physiology; D000076242:mTOR Associated Protein, LST8 Homolog
D048868:Adaptor Proteins, Signal Transducing; D000682:Amyloid; C555285:MLST8 protein, human; D053763:Presenilins; D000076242:mTOR Associated Protein, LST8 Homolog
Alzheimer’s disease; Amyloid; Cell cycle regulation; Endo-lysosomal trafficking; Neuronal survival; Presenilin; Synaptic plasticity