Is it all about Contact? Neurodegeneration as a “Protein Freeze Tag Game” Inside the Central Nervous System

the cause of propagation of misfolded proteins in spongiform encephalopathies. In fact, several recent studies (Jucker and Walker, 2011; Hall and Patuto, 2012; Kanouchi et al., 2012) have suggested that the basic proteins implied in a variety of neurodegenerative diseases [like betaamyloid and tau proteins in Alzheimer’s disease (AD), α-synuclein in Parkinson Disease and dementia with Lewy bodies, polyglutamine proteins in Huntington’s disease and spinocerebellar ataxia, and superoxide dismutase 1 in amyotrophic lateral sclerosis] may share important similarities with the mammalian prion protein (PrP) involved in spongiform encephalopathies, such as the ability to translocate between neurons and further recruit normal proteins to aggregate. The first suggestion of such possibility came from studies that demonstrated that a prion-like propagation mechanism of systemic amyloidoses occurred in animals through fecal transmission (Zhang et al., 2008). As several similarities exist between the pathophysiology of systemic and CNS amyloidoses, there has been a growing interest in the experimental evaluation of a possible protein-to-protein contact-induced transmission as the pathophysiological explanation for the progression of neurodegenerative diseases. In a recent report Liu et al. (2012) described a new experimental protocol for the study of AD which involves a transgenic mouse that differentially expresses pathological human tau protein. In such animal model the authors demonstrated propagation of the pathological tau protein from the mesial portion of the entorhinal cortex into the CA1 region of the hippocampus and the dentate gyrus granule cells. Such findings strongly support a trans-synaptic mechanism of tau protein spreading between neurons along anatomically connected networks. A commentary on