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Outline
Proteostasis is the fundamental process by which cells maintain their normal functions. It involves maintaining the dynamic equilibrium of protein synthesis, folding, transport, and degradation. Disruption of proteostasis leads to the accumulation of misfolded proteins and a deficiency of functional proteins, triggering a pathological cascade—a hallmark of various diseases. Traditional drug development primarily focuses on inhibiting the activity of disease-causing proteins. However, many proteins are considered "undruggable" due to the absence of well-defined binding sites or functional redundancy. Recently, the targeted protein degradation (TPD) has provided a novel therapeutic strategy for traditionally undruggable targets. In this review, we systematically analyze how TPD overcomes the limitations of undruggable targets by remodeling the proteostatic network, covering the classification of protein degradation technologies, molecular mechanisms, and disease applications. Furthermore, we explore the clinical translation potential of TPD technologies, providing novel therapeutic strategies and theoretical frameworks for complex diseases.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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