title: Histochemical approaches to assess cell-to-cell transmission of misfolded proteins in neurodegenerative diseases.
abstract: Formation, aggregation and transmission of abnormal proteins are common features in neurodegenerative disorders including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and Huntington's disease. The mechanisms underlying protein alterations in neurodegenerative diseases remain controversial. Novel findings highlighted altered protein clearing systems as common biochemical pathways which generate protein misfolding, which in turn causes protein aggregation and protein spreading. In fact, proteinaceous aggregates are prone to cell-to-cell propagation. This is reminiscent of what happens in prion disorders, where the prion protein misfolds thus forming aggregates which spread to neighbouring cells. For this reason, the term prionoids is currently used to emphasize how several misfolded proteins are transmitted in neurodegenerative diseases following this prion-like pattern. Histochemical techniques including the use of specific antibodies covering both light and electron microscopy offer a powerful tool to describe these phenomena and investigate specific molecular steps. These include: prion like protein alterations; glycation of prion-like altered proteins to form advanced glycation end-products (AGEs); mechanisms of extracellular secretion; interaction of AGEs with specific receptors placed on neighbouring cells (RAGEs). The present manuscript comments on these phenomena aimed to provide a consistent scenario of the available histochemical approaches to dissect each specific step.
authors.affiliation: Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Natale
authors.forename: E
authors.initials: E
authors.lastname: Pompili
authors.forename: F
authors.initials: F
authors.lastname: Biagioni
authors.forename: S
authors.initials: S
authors.lastname: Paparelli
authors.forename: P
authors.initials: P
authors.lastname: Lenzi
authors.forename: F
authors.initials: F
authors.lastname: Fornai
mesh_terms: D000818:Animals; D002450:Cell Communication; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000401:mortality* / Q000473:pathology; D011328:Prions / Q000378:metabolism* / Q000472:pathogenicity; D017510:Protein Folding; D057165:Proteostasis Deficiencies / Q000401:mortality* / Q000473:pathology
chemical_list: D017127:Glycation End Products, Advanced; D011328:Prions
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