Advancing Neuroscience: The Critical Role of High-Quality Antibodies in Neurodegenerative Research

By Dr. Priyom Bose, Ph.D.Reviewed by Lily Ramsey, LLM

Neuroscience research generally uses antibodies to label, capture, and modulate the functions of target proteins.¹ Antibodies are crucial in research associated with neurodegenerative disorders, particularly in understanding the underlying mechanisms for disease progression, diagnosis, and treatment.²

For instance, antibodies can selectively remove rogue proteins in the brain that influence neurodegenerative diseases.

Image Credit: Prrrettty/Shutterstock.com

Antibodies in Neuroscience Research

Antibodies are immunoglobulin (Ig) proteins that are commonly used in neuroscience research. These proteins are used in research because of their stability, high affinity, and selective binding to the target.³

Since antibodies are resistant to misfolding and degradation, they can be easily produced, purified, and stored in a laboratory.¹ Among the different immunoglobulin types, IgG is used mostly in neuroscience research. Structurally, IgG is a heterodimer, which is composed of two heavy (H) and two light (L) chains.⁴

Recombinant antibodies are immunoglobulins whose codons have been cloned into expression plasmids and introduced into mammalian or Escherichia coli expression systems.¹ This strategy promotes the synthesis of unlimited recombinant antibodies.

Recombinant monoclonal antibodies (mAbs) were initially developed for therapeutic purposes. In comparison to conventional antibodies, recombinant antibodies had been slow to infiltrate research.

Recently, the use of these antibodies in neuroscience research has grown due to their higher reliability, lesser variable expression, and opportunity for further engineering.

Recombinant antibodies can be modified to change the specificity of secondary antibody binding. Short sequences, such as Halo or sortase tags or epitope tags, can be added for direct site-specific labeling of the antibody.⁵ Fluorescent organic molecules or biotin are often used to label antibodies for research purposes.⁶

Monoclonal Antibodies vs Polyclonal Antibodies

The Role of Antibodies in Neurodegenerative Research

Neurodegenerative diseases, such as epileptic encephalopathy, amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), and Parkinson’s disease (PD), threaten the lives of millions of people, partially due to the availability of treatments with minimal efficacy.⁷

At present, a tremendous amount of research time and funds are invested in this area to understand these diseases better and formulate effective therapies.

Interestingly, most neurodegenerative diseases share common pathogenic mechanisms. The majority of neurodegenerative diseases are associated with loss of neuronal connectivity and progressive damage to neuronal cells, which ultimately impairs mobility and cognition.⁸

Protein aggregation, including amyloid aggregation in the nervous system that results from oligomerization and misfolding, are considered a hallmark of many neurodegenerative diseases.

In PD, immune cells accumulate in response to abnormal protein aggregates or neuronal death. In AD, the protein tau (MAPT) accumulates as neurofibrillary tangles within cells, and transmembrane protein Aβ precursor protein (APP) deposits as plaque in the temporal and parietal brain regions.

Antibodies produced via active immunization or passively introduced can bind to protein assemblies that are biomarkers for diseases. Subsequently, it inactivates the protein by neutralization, sequestration, or FcR-mediated effector functions.

Antibodies are important reagents in neuroscience research because they help study proteins involved in the pathogenesis of neurodegenerative diseases. These antibodies can be used to diagnose these diseases early. Neuroscientists identify specific antibodies that are highly sensitive against the potential disease target.

Multiple underlying mechanisms have been uncovered regarding how antibodies may deplete aggregated proteins in the brain. For instance, the peripheral sink hypothesis suggests that antibodies binding to targets in the periphery might alter dynamics across the blood-brain barrier (BBB) and cause a reduction of cerebral antigens.⁹

Solanezumab and ponezumab are mAbs that can selectively target monomeric amyloid-β peptides via the peripheral sink mechanism.¹⁰ Antibodies also exert potent neutralizing responses against viruses in cell-based systems.

More research is required to understand the exact mechanism, which could provide a route to novel therapies in age-related neurodegenerative diseases.

Commercially Manufactured High-Quality Antibodies for Neuroscience Research

Many companies across the world, including EnCor, Thermo Fisher, Novus Biologicals, Bio‐Rad Laboratories, Cell Signaling Technologies, BD Biosciences, BioMedica Diagnostics, and Abcam, provide neuroscientists with high-quality antibodies for experiments.

They manufacture superior quality anti‐human transcription factor (TF) monoclonal and polyclonal antibodies that are immensely beneficial to research. The availability of high-quality antibodies has offered reliability to experimental findings.

Thermo Fisher Scientific has developed antibodies against three key targets, namely, synaptosomal-associated protein (SNAP25), vesicle-associated membrane protein-1 (VAMP), and optineurin (OPTN).

For instance, a disrupted OPTN protein is commonly detected in multiple neurodegenerative diseases, including ALS and glaucoma. SNAP25 and VAMP1 are proteins that are involved with the vesicular transport of neurotransmitters across synapses.

To validate the specificity of Invitrogen SNAP25 mAbs, scientists used the PC12 cell line and were able to detect the precise position of the proteins in the hippocampal membrane and presynaptic terminals. OPTN monoclonal antibody was used to distinctively localize OPTN in the retinal ganglion cells (RGCs).¹¹

EnCor is a well-known American biotech company that manufactures unique, and well-characterized antibody reagents for clinical, biopharmaceutical, and academic research. It manufactures antibodies, namely, MCA-1B7 and RPCA-Fox3, against neuronal nuclei (NeuN), which is a protein found in the nervous system of vertebrates.

EnCor also manufactures MCA-6H63 and MCA-1D44, which are novel neurofilament NF-L antibodies that can specifically identify degenerating neurons and processes. They also provide RPCA-NF-L-ct and MCA-DA2 that can only bind with undamaged neuronal material.¹²

The availability of these high-quality, specific antibodies for both academic and clinical research associated with neurodegenerative diseases has potentially accelerated the process of formulating effective therapeutic interventions for these diseases.

References

1. Trimmer JS. Recombinant Antibodies in Basic Neuroscience Research. Curr Protoc Neurosci. 2020;94(1):e106. doi: 10.1002/cpns.106.
2. Rhodes KJ, Trimmer JS. Antibodies as valuable neuroscience research tools versus reagents of mass distraction. J Neurosci. 2006;26(31):8017-20. doi: 10.1523/JNEUROSCI.2728-06.2006.
3. Chiu ML, et al. Antibody Structure and Function: The Basis for Engineering Therapeutics. Antibodies (Basel). 2019;8(4):55. doi: 10.3390/antib8040055.
4. Schroeder HW Jr, Cavacini L. Structure and function of immunoglobulins. J Allergy Clin Immunol. 2010;125(2):41-52. doi: 10.1016/j.jaci.2009.09.046.
5. Pao PJ, et al. Structural basis of an epitope tagging system derived from Haloarcula marismortui bacteriorhodopsin I D94N and its monoclonal antibody GD-26. FEBS J. 2022;289(3):730-747. doi: 10.1111/febs.16184.
6. Nath N, Godat B, Urh M. Antibody Labeling with Fluorescent Dyes Using Magnetic Protein A and Protein G Beads. J Vis Exp. 2016;(115):54545. doi: 10.3791/54545.
7. Lamptey RNL, et al. A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Nanotherapeutics. Int J Mol Sci. 2022;23(3):1851. doi: 10.3390/ijms23031851.
8. Gadhave DG, et al. Neurodegenerative disorders: Mechanisms of degeneration and therapeutic approaches with their clinical relevance. Ageing Res Rev. 2024;99:102357. doi: 10.1016/j.arr.2024.102357.
9. Yu YJ, Watts RJ. Developing therapeutic antibodies for neurodegenerative disease. Neurotherapeutics. 2013;10(3):459-72. doi: 10.1007/s13311-013-0187-4.
10. van Dyck CH. Anti-Amyloid-β Monoclonal Antibodies for Alzheimer's Disease: Pitfalls and Promise. Biol Psychiatry. 2018;83(4):311-319. doi: 10.1016/j.biopsych.2017.08.010.
11. Thermo Fischer Scientific. Overview of Neurobiology Antibody Applications. https://www.thermofisher.com/uk/en/home/life-science/antibodies/antibodies-learning-center/antibodies-resource-library/antibody-methods/overview-neurobiology-antibody-applications.html. Assessed on October 5, 2024.
12. Encor Biotechnology Inc. https://encorbio.com/. Assessed on October 5, 2024.

Further Reading

• All Neuroscience Content
• Neuroscience vs Neurology: What is the difference?