Muteins of the pyrroline-5-carboxylate reductase 1

A method of identifying a compound capable of modifying the activity of a PYCR1 mutein, the method comprising:

• contacting a compound of interest with the mutein of pyrroline-5-carboxylate reductase 1 (PYCR1) or a nucleic acid molecule encoding a mutein of PYCR1, and
• b. measuring the activity of the PYCR1 mutein,
• whereby the PYCR1 mutein comprises or consists of an amino acid sequence wherein at least one of the amino acid residue corresponding to sequence positions 4, 119, 179, 189, 206, 251, 257 and 266 of the wild type amino acid sequence of PYCR1 as set forth in SEQ ID NO 4 is mutated and leads to a reduced function or loss of function of the mutein compared to the wild-type protein, wherein the amino acid residue at sequence position 251 is replaced by histidine.

A method of modifying the activity of a pyrroline-5-carboxylate reductase (PYCR1) mutein in an cell, the method comprising administering to the cell a compound capable of modifying the activity of the PYCR1 mutein.

A nucleic acid molecule comprising a nucleotide sequence encoding a pyrroline-5-carboxylate reductase 1 (PYCR1) mutein comprising or consisting of an amino acid sequence wherein at least one of the amino acid residue corresponding to sequence positions 4, 119, 179, 189, 206, 251, 257 and 266 of the wild type amino acid sequence of PYCR1 as set forth in SEQ ID NO. 4.

A method of determining in a subject a predisposition of having an age-related disorder associated with pyrroline-5-carboxylate reductase 1 (PYCR1), the method comprising analyzing a nucleic add sample obtained from a subject for the presence of a nucleotide sequence encoding a mutein comprising or consisting of an amino add sequence wherein at least one of the amino acid residue corresponding to sequence positions 4, 119, 179, 189, 206, 251, 257 and 266 of the wild type amino add sequence of PYCR1 as set forth in SEQ ID NO. 4, wherein the presence of the nucleotide sequence indicates a predisposition of the subject having or being at risk for having the age-related disorder.

A method of using a nucleic acid molecule comprising a nucleotide sequence encoding a mutein comprising or consisting of an amino acid sequence wherein at least one of the amino acid residue corresponding to sequence positions 4, 119, 179, 189, 206, 251, 257 and 266 of the wild type amino acid sequence of PYCR1 as set forth in SEQ ID NO. 4 for diagnosing or determining a predisposition of having an age-related disorder associated with PYCR1.

A method of treating a subject having an age-related disorder associated with PYCR1 or being at risk to develop an age-related disorder associated with PYCR1, the method comprising introducing a nucleic add molecule comprising a nucleotide sequence encoding pyrroline-5-carboxylate reductase 1 (PYCR1) or a functional fragment or functional mutant thereof into the subject.

A method of treating a subject having an age-related disorder associated with PYCR1 or being at risk to develop an age-related disorder associated with PYCR1, the method comprising administering to the subject a compound capable of modifying the activity of a PYCR1 mutein.