Abstract: There is provided a method of reducing neuronal microtubule binding protein Tau (Tau) levels, promoting neuronal Tau degradation and/or promoting neuronal survival, in a subject in need thereof comprising contacting the subjects neurons with an effective amount of an agent that increases a long phosphotyrosine-binding (PTB) Numb isoform expression and/or activity, whereby neural Tau levels is reduced in the presence of the agent, the neuronal Tau degradation is promoted and/or the neuronal survival is promoted as compared to in the absence thereof. Also provided are methods of stratification based on PTB Numb isoform expression and/or activity of the subjects and compositions and kits for applying the methods.

Abstract: There is provided a method of reducing neuronal microtubule binding protein Tau (Tau) levels, promoting neuronal Tau degradation and/or promoting neuronal survival, in a subject in need thereof comprising contacting the subjects neurons with an effective amount of an agent that increases a long phosphotyrosine-binding (PTB) Numb isoform expression and/or activity, whereby neural Tau levels is reduced in the presence of the agent, the neuronal Tau degradation is promoted and/or the neuronal survival is promoted as compared to in the absence thereof. Also provided are methods of stratification based on PTB Numb isoform expression and/or activity of the subjects and compositions and kits for applying the methods.

Abstract: The instant disclosure provides a recombinant nervous system cell comprising nucleic acid encoding IKAROS Family Zinc Finger 4 (Ikzf4) and/or IKAROS Family Zinc Finger 1 (Ikzf1)); a vector comprising a glial specific promotor operably-linked to a nucleic acid molecule encoding IKAROS Family Zinc Finger 1 (Ikzf1) and/or a nucleic acid molecule encoding IKAROS Family Zinc Finger 4 (Ikzf4); and methods of producing a recombinant cone photoreceptor, comprising: (A) (a) introducing a nucleic acid molecule encoding IKAROS Family Zinc Finger 1 (Ikzf1) in a Müller glia cell; and (b) introducing a nucleic acid molecule encoding IKAROS Family Zinc Finger 4 (Ikzf4) in the Müller glia cell; or (B) introducing a nucleic acid molecule encoding Ikzf4 in a retinal neuroepithelial cell; whereby the retinal neuroepithelial cell or the Müller glia is reprogrammed into a recombinant cone photoreceptor.