In the present invention it is shown that the inactivation of the Pyk2 gene does not alter hippocampal development but prevents hippocampal-dependent memory tasks and LTP. Inventors clearly provide evidence for multiple roles of Pyk2 in spine morphology and postsynaptic structure. Thus, the inventors used direct overexpression of PYK2 by AAV-mediated gene transfer into the brain of Huntington's and Alzheimer's mouse models and found that overexpression of PYK2 in these 2 models improves synaptic properties and spine density deficits which is also accompanied by a rescue of spatial memory. Accordingly it was demonstrated that PYK2 may restore cognitive functions in neurodegenerative diseases. Thus the present invention relates to methods and pharmaceutical compositions for the treatment of neurodegenerative disease. In particular the present invention relates to a method of treating neurodegenerative disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a vector which comprises a nucleic acid molecule encoding for PYK2 polypeptide.

The present invention relates to compounds, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of RIP2 kinase, including degrading RIP2 kinase, the treatment of diseases and conditions mediated by the RIP2 kinase, in particular for the treatment of inflammatory diseases or conditions.

In one aspect, antibodies that specifically bind to a human triggering receptor expressed on myeloid cells 2 (TREM2) protein are provided. In some embodiments, the antibody increases levels of soluble TREM2 (sTREM2). In some embodiments, the antibody decreases levels of sTREM2. In some embodiments, the antibody enhances TREM2 activity. In some embodiments, the antibody inhibits TREM2 activity.

The present invention relates to a polypeptide binding to fibroblast growth factor receptor 3 isoforms 3b and 3c (FGFR3b and FGFR3c), wherein the polypeptide comprises an amino acid sequence selected from the group consisting of: (a) GVTLFVALYDYEVYGPTPMLSFHKGEKFQIL(X.sup.1)(X.sup.2)(X.sup.3) (X.sup.4)GPYWEARSL(X.sup.5)TGETG(X.sup.6)IPSNYVAPVDSIQ (SEQ ID NO: 1), wherein amino acid positions (X1) to (X.sup.6) may be any amino acid sequence; (b) an amino acid sequence which is at least 95% identical to the amino acid sequence of (a), wherein the identity determination excludes amino acid positions (X.sup.1) to (X.sup.6) and provided that the amino acid sequence EVYGPTPM (SEQ ID NO: 2) in amino acid positions 12 to 19 of SEQ ID NO: 1 is conserved and the amino acids P and Y in amino acid positions 37 and 38 of SEQ ID NO: 1 are conserved; (c) GVTLFVALYDYEVMSTTALSFHKGEKF QILSQSPHGQYWEARSLTTGETG(X.sup.6)IPSNYVAPVDSIQ (SEQ ID NO: 19), wherein the amino acid position (X.sup.6) may be any amino acid; and (d) an amino acid sequence which is at least 95% identical to the amino acid sequence of (c), wherein the identity determination excludes amino acid position (X.sup.6) and provided that the amino acid sequences EVMSTTA (SEQ ID NO: 20) in amino acid positions 12 to 18 of SEQ ID NO: 19 and SQSPH (SEQ ID NO: 21) in amino acid positions 31 to 35 of SEQ ID NO: 19 are conserved and the amino acids Q and Yin amino acid positions 37 and 38 of SEQ ID NO: 19 are conserved.

The present invention provides methods for inhibiting Fyn kinase, using 5-3-pyridin-2-amine, 6-3-imidazo[1,2-a] pyrazine, 6-3-imidazo[1,2-b] pyridazine, N-(5-imidazo [2,1-b][1,3,4] thiadiazol-2-yl)-amine, 4-3-1H-pyrazolo[3,4-b] pyridine, and N-(3-imidazo [1,2-b] pyridazin-6-yl) amine compounds and methods of treatment, prevention, inhibition or amelioration of diseases and conditions associated with Fyn kinase using such compounds.

Methods and compositions are described herein that inhibit FAK/ATK interactions. Such methods and compositions are useful for inhibiting cell adhesion and cancer metastasis.

A formulation comprising an ingestible carrier and an isolated strain of Bifidobacterium longum.

The present invention provides compositions and methods for enhancing the radiation resistance of a cell by modulating PKC and methods of preventing or treating radiation-mediated injury.

Described are heat stable protein-phospholipid concentrates within lung surfactant therapeutic compositions for the treatment of respiratory diseases in premature infants, children and adults. The concentrates can be suitable for localized delivery with improved transport to and spreadability within the lung and other tissues resulting in greater efficacy and efficiency of treatment.

The present application, in some embodiments, is directed to a polynucleotide including: (a) a first nucleic acid molecule including a sequence of a human endogenous Bruton's tyrosine kinase (BTK) promoter; and (b) a second nucleic acid molecule including a codon optimized sequence encoding a BTK or a functional analog thereof. Further provided are an expression vector, a cell, and a composition, all of which include the polynucleotide of the invention, and a method of using same, such as for treating X-linked Agammaglobulinemia (XLA) in a subject in need thereof.