Abstract: Non-aggregating protein analogues of proteins involved in a proteinopathy, for example Alzheimer's disease, are provided. The protein has a beta-sheet aggregation domain, and the non-aggregating protein analogue has a beta-sheet destabilizing modification in the beta-sheet aggregation domain but substantially retains wild type protein function. The beta-sheet destabilizing modification can be a substitution of a naturally occurring amino acid for a non-naturally occurring amino acid. Methods of treating a proteinopathy using the non-aggregating protein analogues and methods of designing a non-aggregating protein analogue are provided.

Abstract: The present disclosure relates to a method for determining a risk of development or risk of presence of Alzheimer's disease in a human subject comprising analyzing an activity of a PIEZO1 receptor. The disclosure also relates to a kit for determining a risk of development or risk of presence of Alzheimer's disease according to the present method. The disclosure also relates to an in vitro use of a PIEZO1 receptor as a biomarker and determination of intracellular calcium level as a biomarker for determining a risk of development or risk of presence of Alzheimer's disease in a human subject.

Abstract: The present invention relates to diagnosing, preventing, delaying or reverting the progression of pathologies associated with abnormal amyloid deposits, such as that exemplified by Alzheimer's disease (AD). More specifically, the method involves administration of specific molecules that function as Piezo agonists, such as Yoda1, Jedi1, 5 Jedi2, or functional analogs thereof, that are able to modulate microglial activation towards anti-inflammatory state and/or interfere with the formation of amyloidogenic peptides and/or increase their efflux from the central nervous system.

Abstract: The present invention relates to the fields of life sciences and medicine. Specifically, the invention relates to therapies of neurodegenerative diseases. More specifically, the present invention relates to interleukin-33 (IL-33), a fragment thereof, a polynucleotide encoding IL-33 or a fragment thereof for use in treatment or prevention of a neurodegenerative disease involving inflammation in a subject and to a method of treating or preventing a neurodegenerative disease involving neuroinflammation in a subject. Still, the present invention relates to IL-33, a fragment thereof, a polynucleotide encoding IL-33 or a fragment thereof for use in improving or restoring neuronal function or endogenous neuronal repair mechanisms, or enhancing endogenous neurogenesis, oligodendrogenesis or neuronal differentiation in a subject.

Abstract: The present invention relates to the fields of life sciences and medicine. Specifically, the invention relates to therapies of neurodegenerative diseases. More specifically, the present invention relates to interleukin-33 (IL-33), a fragment thereof, a polynucleotide encoding IL-33 or a fragment thereof for use in treatment or prevention of a neurodegenerative disease involving inflammation in a subject and to a method of treating or preventing a neurodegenerative disease involving neuroinflammation in a subject. Still, the present invention relates to IL-33, a fragment thereof, a polynucleotide encoding IL-33 or a fragment thereof for use in improving or restoring neuronal function or endogenous neuronal repair mechanisms, or enhancing endogenous neurogenesis, oligodendrogenesis or neuronal differentiation in a subject.