Protein engineering can be defined as the modification of protein structure with recombinant DNA technology or chemical treatment to get a desirable function for better use in Medicine, Industry, and Agriculture. We are explaining protein and its role in neurodegenerative disease, majorly protein. Content: 1. Protein Engineering Definition 2. Objective 3. Various areas of Protein Engineering 4. Protein Engineering and Multiple Sclerosis (MS) 5. Interferons (alpha and beta) 6. Interferon beta and MS 7. Interferon beta 1a (Avonex) 8. Interferon beta 1b (Betaseron) 9. Mechanism of action 10. Conclusion

1. PROTEIN
ENGINEERING AND
ITS APPLICATIONS
(HUMAN INTERFERON BETA)
Submitted By:
Gunjit Setia

2. Protein Engineering
- Protein engineering can be defined as the
modification of protein structure with
recombinant DNA technology or chemical
treatment to get a desirable function for better
use in Medicine, Industry and Agriculture.

3. Objectives
To create a superior enzyme to catalyze the production
of high value specific chemicals.
To produce enzyme in large quantities.
To produce biological compounds(include synthetic
peptide, storage protein, and synthetic drugs) superior to
natural one.
Image From: https://gfycat.com/gifs/tag/genetic+engineering

4. Various Areas of Protein Engineering
Image From:
https://www.creativebiomart.net/protein-
engineering-services.htm

5. Protein Engineering and Multiple
Sclerosis
- Multiple sclerosis (MS) is a chronic CNS disease.
- Age group of 20 and 40 years.
- Characterized by intermittent attacks and neurological symptoms.
- Relapsing-remitting multiple sclerosis to secondary progress multiple sclerosis.
- Multifactorial disease including factors such as environment, genetics, and virus infection.
- Different therapeutic efforts have been developed for treatment of MS patients including
interferon beta (IFNβ), mitoxantrone, glatiramer, and natalizumab which have critical roles
in modulating inflammation, improving immune self-regulation, restoring blood–brain
barrier (BBB) integrity, and increasing damage repair.
- IFNβ has demonstrated advantageous effects on decreasing clinical disease activity and it
also described as an important treatment for MS.
Image from: https://medlineplus.gov/ency/article/000737.htm

6. IFN alpha and IFN beta
- The family of Type I interferons, which include the Interferon-alpha (IFN-α) proteins
and Interferon-beta (IFN-β), are secreted by many cell types including macrophages,
lymphocytes, fibroblasts, endothelial cells and others.
- They stimulate cells of the immune system including both macrophages and NK cells to
form an antiviral response, and they have also been shown to be active against tumors.
- IFN-β is known to also be produced in the central nervous system (CNS) by both the
glial cells and astrocytes.
Image From: https://www.researchgate.net/figure/Interferon-protein-structures-
Interferons-alpha-and-beta-the-type-I-interferons-have-a_fig1_221929527

7. IFNβ and Multiple Sclerosis
- The biological effects of IFNβ as a pleiotropic cytokine
occurred through its binding to IFNβ receptor (IFNAR)1 and 2
subunits of heterodimeric cell surface receptor complex.
- Recombinant forms of IFNβ including interferon β-1b
(Betaseron) and interferon β-1a (Avonex) are among the first
Food and Drug Administration-approved drugs and the first-
line therapies for MS treatment.
Image From: https://www.rebif.com/hcp/home/how-rebif-works.html

8. Human Interferon Beta 1a (Avonex)
- Interferon beta-1a is a form of recombinant human interferon used to slow disease
progression and reduce the frequency of clinical symptoms in patients who have relapsing
multiple sclerosis.
- Human interferon beta (166 residues), glycosylated, MW=22.5kD. It is produced by
mammalian cells (Chinese Hamster Ovary cells) into which the human interferon beta gene
has been introduced. The amino acid sequence is identical to that of natural human
interferon beta.
- Protein Chemical FormulaC908H1408N246O252S7
Image From: https://go.drugbank.com/drugs/DB00060

9. Human Interferon Beta 1b (Betaseron)
- Interferon beta-1b is a form of recombinant human interferon used to slow the
progression of relapsing multiple sclerosis and to reduce the frequency of
clinical symptoms
- Human interferon beta (165 residues), cysteine 17 is substituted with serine.
Produced in E. coli, no carbohydrates, MW=18.5kD
- Protein Chemical Formula [C908H1408N246O253S6]
Image From: https://go.drugbank.com/drugs/DB00068

10. Mechanism of action

11. Mechanism Explained
- Interferon beta binds to type I interferon receptors (IFNAR1 and IFNAR2c) which activate two Jak (Janus
kinase) tyrosine kinases (Jak1 and Tyk2).
- These trans phosphorylate themselves and phosphorylate the receptors.
- The phosphorylated INFAR receptors then bind to Stat1 and Stat2 (signal transducers and activators of
transcription) which dimerize and activate multiple (~100) immunomodulatory and antiviral proteins.
- Interferon beta binds more stably to type I interferon receptors than interferon alpha.

12. Conclusion
IFNβ therapy plays an important role in the treatment of patients with MS. Interferons have been
shown to improve clinical outcomes, and their long-term safety profiles make them standard-of-
care, first-line therapy for MS. Although patients with RRMS may benefit from interferon
treatment, individual response, in terms of both efficacy and Adverse Events, is unpredictable,
and it is necessary in many cases to switch treatments to stabilize disease.

13. References
- Runkel, L., Meier, W., Pepinsky, R. B., Karpusas, M., Whitty, A., Kimball, K., ... & Goelz, S. E. (1998). Structural and
functional differences between glycosylated and non-glycosylated forms of human interferon-β (IFN-β). Pharmaceutical
research, 15(4), 641-649.
- https://www.iodine.com/compare/betaseron-vs-avonex
- https://www.differencebetween.com/difference-between-interferon-beta-1a-and-vs-1b/
- https://pediaa.com/what-is-the-difference-between-interferon-beta-1a-and-1b/
- Jankovic, S. M. (2010). Injectable interferon beta-1b for the treatment of relapsing forms of multiple sclerosis. Journal of
inflammation research, 25-31.
- Kieseier, B. C. (2011). The mechanism of action of interferon-β in relapsing multiple sclerosis. CNS drugs, 25(6), 491-
502.
- Hervas-Stubbs, S., Perez-Gracia, J. L., Rouzaut, A., Sanmamed, M. F., Le Bon, A., & Melero, I. (2011). Direct effects of
type I interferons on cells of the immune system. Clinical Cancer Research, 17(9), 2619-2627.