Levetiracetam prevents Aβ production through SV2a-dependent modulation of App processing in Alzheimer's disease models.

In Alzheimer's disease (AD), amyloid-beta (Aβ) peptides are produced by proteolytic cleavage of the amyloid precursor protein (APP), which can occur during synaptic vesicle (SV) cycling at presynapses. Precisely how amyloidogenic APP processing may impair presynaptic proteostasis and how to therapeutically target this process remains poorly understood. Using knock-in mouse models of early Aβ pathology, we found proteins with hampered degradation accumulate at presynaptic sites.

Neuroprotective effect and potential of cellular prion protein and its cleavage products for treatment of neurodegenerative disorders part I. a literature review.

Introduction: The cellular prion protein (PrP) is well known for its pathogenic roles in prion diseases, several other neurodegenerative diseases (such as Alzheimer's disease), and multiple types of cancer, but the beneficial aspects of PrP and its cleavage products received much less attention.

Areas Covered: Here the authors will systematically review the literatures on the negative as well as protective aspects of PrP and its derivatives (especially PrP N-terminal N1 peptide and shed PrP). The authors will dissect the current findings on N1 and shed PrP, including evidence for their neuroprotective effects, the categories of PrP cleavage, and numerous cleavage enzymes involved.

Neuroprotective effect and potential of cellular prion protein and its cleavage products for treatment of neurodegenerative disorders part II: strategies for therapeutics development.

The cellular prion protein (PrP), some of its derivatives (especially PrP N-terminal N1 peptide and shed PrP), and PrP-containing exosomes have strong neuroprotective activities, which have been reviewed in the companion article (Part I) and are briefly summarized here. We propose that elevating the extracellular levels of a protective PrP form using gene therapy and other approaches is a very promising novel avenue for prophylactic and therapeutic treatments against prion disease, Alzheimer's disease, and several other neurodegenerative diseases. We will dissect the pros and cons of various potential PrP-based treatment options and propose a few strategies that are more likely to succeed.