Current Progress in the Development of Probes for Targeting α-Synuclein Aggregates

Area of Science:

• Neuroscience
• Biochemistry
• Medical Imaging

Background:

• Alpha-synuclein (α-synuclein) aggregation into intracellular inclusions is a hallmark of Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).
• Accurate tracking of α-synuclein is vital for early diagnosis, disease monitoring, and therapeutic development in these neurodegenerative conditions.

Purpose of the Study:

• To provide a comprehensive overview of potential α-synuclein targeting probes developed over the past two decades.
• To assess the current status, properties, and development strategies of small-molecule α-synuclein imaging probes.

Main Methods:

• Review of scientific literature focusing on small-molecule fluorescent probes and radiolabeled probes for α-synuclein imaging.
• Analysis of probe properties, development strategies, and reported progress in the field.

Main Results:

• Significant research has explored various α-synuclein targeting probes, including fluorescent and radiolabeled agents.
• Despite progress, no α-synuclein targeting probes have achieved widespread clinical application to date.
• Key properties of promising imaging molecules and strategies for developing new probes have been identified.

Conclusions:

• The development of effective α-synuclein targeting probes remains a critical challenge in neurodegenerative disease research.
• Further advancements in probe design and validation are needed to facilitate clinical translation for PD, DLB, and MSA.
• This review offers insights into the current landscape and future prospects for α-synuclein imaging probe development.