Recent advances in the understanding of the role of synaptic proteins in Alzheimer's Disease and other neurodegenerative disorders

Article type: Research Article

Authors: Masliah, Eliezer^{; *}

Affiliations: Departments of Neurosciences and Pathology University of California San Diego, School of Medicine La Jolla, California 92093, USA

Correspondence: [*] Correspondence to: Dr. E. Masliah, Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093-0624, USA. Tel.: +1 858 534 8992; Fax: +1 858 534 6232; E-mail: emasliah@ucsd.edu

Abstract: Synaptic damage is an early pathological event common to many neurodegenerative disorders such as Alzheimer's disease (AD) and is the best correlate to the cognitive impairment. Several molecules involved in AD and in other neurodegenerative disorders play an important role in synaptic function and when misfolded aggregate and form amyloid fibrils. Synaptic proteins with an amyloid domain include amyloid ß-protein precursor, prion protein, huntingtin, ataxin-1 and α-synuclein. Two of the possible mechanisms by which alterations in synaptic proteins lead to synapse damage are: 1) misfolded or aggregated synaptic molecules have lost their normal function and/or 2) they have gained a toxic capacity. Recent studies support the possibility that while oligomers are toxic, polymers might be inactive. The mechanisms by which oligomers trigger synapse loss could be related to their ability to triggers stress signals once they enter the nucleus and/or accumulate at the endoplasmic reticulum.

DOI: 10.3233/JAD-2001-3117

Journal: Journal of Alzheimer's Disease, vol. 3, no. 1, pp. 121-129, 2001