Using Xenopus oocytes in neurological disease drug discovery

ABSTRACT

Introduction: Neurological diseases present a difficult challenge in drug discovery. Many of the current treatments have limited efficiency or result in a variety of debilitating side effects. The search of new therapies is of a paramount importance, since the number of patients that require a better treatment is growing rapidly. As an in vitro model, Xenopus oocytes provide the drug developer with many distinct advantages, including size, durability, and efficiency in exogenous protein expression. However, there is an increasing need to refine the recent breakthroughs.

Areas covered: This review covers the usage and recent advancements of Xenopus oocytes for drug discovery in neurological diseases from expression and functional measurement techniques to current applications in Alzheimer’s disease, painful neuropathies, and amyotrophic lateral sclerosis (ALS). The existing limitations of Xenopus oocytes in drug discovery are also discussed.

Expert opinion: With the rise of aging population and neurological disorders, Xenopus oocytes, will continue to play an important role in understanding the mechanism of the disease, identification and validation of novel molecular targets, and drug screening, providing high-quality data despite the technical limitations. With further advances in oocytes-related techniques toward an accurate modeling of the disease, the diagnostics and treatment of neuropathologies will be becoming increasing personalized.

KEYWORDS:

• Xenopus oocytes
• neurological diseases
• electrophysiology
• patch clamping
• ion channels
• chronic pain
• CIPN
• Alzheimer
• ALS

Article highlights

• Xenopus oocytes offer unique advantages as an animal model for neurological disease drug discovery as they contain few endogenous ion channels and can effectively translate exogenous proteins.

• Due to their size and durability, Xenopus oocytes provide an ease of use for many electrophysiological techniques as well as high-throughput experimentation.

• Novel protein expression techniques allow for the direct transplantation and examination of malfunctioning ion channels from tissue samples into Xenopus oocytes, which provide a more individualized approach to studying disease.

• Xenopus oocytes continue to play major roles in the development of drugs targeting many neurological diseases, including Alzheimer's disease, amyotrophic lateral sclerosis, and chronic pain among others.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors thanks grants from the National Institutes of Health (NIH) [R01 CA208623] and from the National Science Foundation (NSF) award [#1827656] for funding support.