Abstract: The NF-E2-related factor 2 (Nrf2) is a key transcriptional regulator of antioxidant defense and detoxification. To directly monitor stabilization of Nrf2 we fused its Neh2 domain, responsible for the interaction with its nucleocytoplasmic regulator, Keap1, to firefly luciferase (Neh2-luciferase). It is shown herein that Neh2 domain is sufficient for recognition, ubiquitination and proteasomal degradation of Neh2-luciferase fusion protein. The novel Neh2-luc reporter system allows direct monitoring of the adaptive response to redox stress and classification of drugs based on the time-course of reporter activation. The novel reporter was used to screen a library of compounds to identify activators of Nrf2. The most robust and yet non toxic Nrf2 activators found—nordihydroguaiaretic acid, fisetin, and gedunin-induced astrocyte-dependent neuroprotection from oxidative stress via an Nrf2-dependent mechanism.

Abstract: The NF-E2-related factor 2 (Nrf2) is a key transcriptional regulator of antioxidant defense and detoxification. To directly monitor stabilization of Nrf2 we fused its Neh2 domain, responsible for the interaction with its nucleocytoplasmic regulator, Keap1, to firefly luciferase (Neh2-luciferase). It is shown herein that Neh2 domain is sufficient for recognition, ubiquitination and proteasomal degradation of Neh2-luciferase fusion protein. The novel Neh2-luc reporter system allows direct monitoring of the adaptive response to redox stress and classification of drugs based on the time-course of reporter activation. The novel reporter was used to screen a library of compounds to identify activators of Nrf2. The most robust and yet non toxic Nrf2 activators found—nordihydroguaiaretic acid, fisetin, and gedunin-induced astrocyte-dependent neuroprotection from oxidative stress via an Nrf2-dependent mechanism.

Abstract: A method of stimulating neurite outgrowth in a subject may include administering to the subject a formulation that includes a tctex-1-related polypeptide that stimulates neurite outgrowth in vitro.

Abstract: A method of stimulating neurite outgrowth in a subject may include administering to the subject a formulation that includes a tctex-1-related polypeptide that stimulates neurite outgrowth in vitro.

Abstract: A polypeptide may include an amino acid sequence having at least about 95% identity to the amino acid sequence of SEQ ID NO: 42, wherein a residue at position 94 of the polypeptide is an amino acid other than threonine or wherein a residue at position 82 of the polypeptide is an amino acid other than serine. A polypeptide may include at least the first 14 residues and at most the first 92 residues of an amino acid sequence starting with residue 1 of, and having at least about 95% identity to, the amino acid sequence of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 16, or 17. Such polypeptide may stimulate neurite outgrowth or neurogenesis. A nucleic acid may encode the polypeptide. A vector may include the nucleic acid. A host cell, such as an embryonic stem cell, may include the vector.