Background & Objective: Protein misfolding and aggregation have been considered the
common pathological hallmarks for a number of neurodegenerative diseases, including Alzheimer’s
disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). These abnormal proteins aggregates
damage mitochondria and induce oxidative stress, resulting in neuronal cell death. Prolonged
neuronal damage activates microglia and astrocytes, development of inflammation reaction and further
promotes neurodegeneration. Thus, elimination of abnormal protein aggregates without eliciting any
adverse effects are the main treatment strategies. To overcome this, recent studies have deployed single-
chain fragment variable antibodies (scFvs) to target the pathological protein aggregates, such as
amyloid-beta (Aβ) peptides, α-synuclein (α-syn) and Huntingtin (Htt). To date scFv has been effective
at inhibiting abnormal protein aggregates formation in both in vitro and in vivo model system of AD,
PD and HD.
Conclusion: Currently active research is still ongoing to improve the scFv gene delivery technology,
to further enhance brain penetration, intracellular stability, solubility and efficacy of scFv intrabody.