The present disclosure provides a pharmaceutical composition for treating Alzheimer’s disease, which at least includes an extracellular vesicle that is prepared by a method including: a first culturing step: performing an amplification culture of an adipose-derived stem cell in a first culture medium at a cell density of 6,000-15,000 cells/cm.sup.2 until an amplification amount of the adipose-derived stem cell is above 90% of that before the culture; a second culturing step: culturing the amplified adipose-derived stem cell in a second culture medium at a cell density of 10,000-100,000 cells/cm.sup.2 for 20-30 hours; and an extracellular vesicle separating step: collecting a culture solution and separating the extracellular vesicle from the culture solution by utilizing a tangential flow filtration (TFF) or ultrafiltration method.

A bone delivery conjugate having a structure selected from the group consisting of: A) X-D.sub.n-Y-protein-Z; and B) Z-protein-Y-D.sub.n-X, wherein X is absent or is an amino acid sequence of at least one amino acid; Y is absent or is an amino acid sequence of at least one amino acid; Z is absent or is an amino acid sequence of at least one amino acid; and D.sub.n is a poly aspartate wherein n=10 to 16. Compositions comprising same and methods of use thereof.

In certain embodiments, the present disclosure provides compositions and methods for treating protein aggregation-based disorders (e.g., Age-related Macular Degeneration (AMD), Inclusion Body Myositis (IBM), Myofibrillar Myopathy 2 (MFM2), and Nemaline Myopathy (NM)).

Disclosed herein is a method of enhancing the ubiquitin proteasome system (“UPS”) in a subject in need thereof, comprising administering an effective amount of a composition comprising neprilysin and a cell targeting moiety, wherein administration of the composition delivers the composition into the intracellular space of one or more cells of the subject and wherein the subject suffers from a condition associated with a UPS deficiency.

This disclosure relates to compositions and methods of reversing senescence in T cells by interrupting vasoactive intestinal peptide (VIP) signaling and/or inhibiting phosphatidylinositol-3-kinase (PI3 kinase) inhibitor signaling and uses in managing cancer and chronic viral infections. In certain embodiments, the disclosure contemplates methods of reversing T cell senescence by mixing T cell in vitro with an agent that prevents VIP from interacting with VIP receptors and/or a PI3 Kinase inhibitor. In certain embodiments, the disclosure contemplates the expansion of senescent T cells by mixing with a PI3 kinase inhibitor, an agent that block VIP and VIP receptor signaling, a VIP degrading enzyme, and combinations thereof.

This invention is directed to methods and compositions for increasing the expression or activity of neprilysin in, for example, the frontal cortex or the entorhinal cortex using a progranulin polypeptide or effector. The present invention is further directed to methods of reducing microglia in the brain of a patient with neurodegenerative disease using a progranulin polypeptide or effector.

This invention is directed to methods and compositions for increasing the expression or activity of neprilysin in, for example, the frontal cortex or the entorhinal cortex using a progranulin polypeptide or effector. The present invention is further directed to methods of reducing microglia in the brain of a patient with neurodegenerative disease using a progranulin polypeptide or effector.

This disclosure relates to compositions and methods of reversing senescence in T cells by interrupting vasoactive intestinal peptide (VIP) signaling and/or inhibiting phosphatidylinositol-3-kinase (PI3 kinase) inhibitor signaling and uses in managing cancer and chronic viral infections. In certain embodiments, the disclosure contemplates methods of reversing T cell senescence by mixing T cell in vitro with an agent that prevents VIP from interacting with VIP receptors and/or a PI3 Kinase inhibitor. In certain embodiments, the disclosure contemplates the expansion of senescent T cells by mixing with a PI3 kinase inhibitor, an agent that block VIP and VIP receptor signaling, a VIP degrading enzyme, and combinations thereof.

A bone delivery conjugate having a structure selected from the group consisting of: A) X-D.sub.n-Y-protein-Z; and B) Z-protein-Y-D.sub.n-X, wherein X is absent or is an amino acid sequence of at least one amino acid; Y is absent or is an amino acid sequence of at least one amino acid; Z is absent or is an amino acid sequence of at least one amino acid; and D.sub.n is a poly aspartate wherein n=10 to 16. Compositions comprising same and methods of use thereof.

This disclosure relates to compositions and methods of reversing senescence in T cells by interrupting vasoactive intestinal peptide (VIP) signalling and/or inhibiting phosphatidylinositol-3-kinase (PI3 kinase) inhibitor signalling and uses in managing cancer and chronic viral infections. In certain embodiments, the disclosure contemplates methods of reversing T cell senescence by mixing T cell in vitro with an agent that prevents VIP from interacting with VIP receptors and/or a PI3 Kinase inhibitor. In certain embodiments, the disclosure contemplates the expansion of senescent T cells by mixing with a PI3 kinase inhibitor, an agent that block VIP and VIP receptor signalling, a VIP degrading enzyme, and combinations thereof.