Huntingtin (HTT) antibodies are essential tools for studying the HTT protein, which is encoded by the *HTT* gene and plays a critical role in Huntington’s disease (HD), a fatal neurodegenerative disorder. The mutation underlying HD involves an abnormal expansion of CAG repeats in the *HTT* gene, leading to a toxic, aggregation-prone mutant HTT protein (mHTT) with an extended polyglutamine (polyQ) tract. Wild-type HTT is implicated in various cellular functions, including vesicle transport, synaptic signaling, and neuroprotection, while mHTT disrupts these processes, causing neuronal dysfunction and death.
HTT antibodies are designed to detect specific regions or modifications of the HTT protein, such as the N-terminus, C-terminus, or polyQ domain. They are widely used in research applications like Western blotting, immunohistochemistry, and ELISA to analyze HTT expression, localization, and aggregation in cellular and animal models. Some antibodies differentiate between wild-type and mutant HTT, enabling studies on disease mechanisms or therapeutic efficacy. For instance, they help evaluate therapies aimed at reducing mHTT levels, such as antisense oligonucleotides or gene-editing approaches.
Challenges in HTT antibody development include ensuring specificity due to homology with other proteins and distinguishing between normal and expanded polyQ regions. Additionally, post-translational modifications (e.g., phosphorylation) or proteolytic fragments of HTT require tailored antibodies. These reagents remain vital for advancing HD research and therapeutic development.