Behavioural assay

• Main Authors: Douglas Armstrong, Wayne Davies, Lysimachos Zografos, Valentina Ferlito
• Format: Patent
• Language: English
• Published: 29.11.2017
• Subjects: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIRCHEMICAL OR PHYSICAL PROPERTIES; MEASURING; PHYSICS; TESTING

A method for measuring effects of drugs on the nervous system is described, with particular application to screening for drugs giving neuroprotection against neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Drosophila are modified genetically to express human wild-type alpha synuclein (UniProt: P37840, Ensembl.ENSG00000145335), or the human alpha synuclein mutants A30P, A53T, E46K, G51D, H50Q, artificial alpha synuclein mutants such as TPαS (A30P, A56P and A76P), or any combination of these, in the larval nervous system. Alternatively Drosophila are modified genetically to express human Abeta42 Arctic peptide (E693G: derived from the "Arctic" E693G form of the Amyloid beta precursor protein, UniProt P05067, encoded by the APP gene Ensembl.ENSG00000142192, Nilsberth C. et al., 2001 Nature Neuroscience 4, 887-893), or other forms of the Abeta peptide in the larval nervous system, whether expressed directly or derived from human APP. Larvae, for example third instar, from these genetically modified Drosophila are observed in a standard growth medium with or without addition of a chemical compound: wild-type larvae ideally with the same genetic background are used as controls. The observations determine whether the chemical compound changes the speed of movement of the larvae. The assay methods and related articles of composition can be used to assess the modification by chemical compounds of the actions of the human toxic proteins alpha synuclein and Abeta42 on nerve cell function and behaviour. The assay constitutes a method to screen for chemical compounds that are neuroprotective in Alzheimer's or Parkinson's disease and other neurodegenerative diseases.