Protein tyrosine phosphatase 1B (PTP1B) is a typical member of the PTP family, considered a direct negative regulator of several receptor and receptor-associated tyrosine kinases. This widely localized enzyme has been involved in the pathophysiology of several diseases. More recently, PTP1B has attracted attention in the field of neuroscience, since its activation in brain cells can lead to schizophrenia-like behaviour deficits, anxiety-like effects, neurodegeneration, neuroinflammation and depression. Conversely, PTP1B inhibition has been shown to prevent microglial activation, thus exerting a potent anti-inflammatory effect and has also shown potential to increase the cognitive process through the stimulation of hippocampal insulin, leptin and BDNF/TrkB receptors. Notwithstanding, most research on the clinical efficacy of targeting PTP1B has been developed in the field of obesity and type 2 diabetes mellitus (TD2M). However, despite the link existing between these metabolic alterations and neurodegeneration, no clinical trials assessing the neurological advantages of PTP1B inhibition have been performed yet. Preclinical studies, though, have provided strong evidence that targeting PTP1B could allow to reach different pathophysiological mechanisms at once. herefore, specific interventions or trials should be designed to modulate PTP1B activity in brain, since it is a promising strategy to decelerate or prevent neurodegeneration in aged individuals, among other neurological diseases. The present paper fails to include all neurological conditions in which PTP1B could have a role; instead, it focuses on those which have been related to metabolic alterations and neurodegenerative processes. Moreover, only preclinical data is discussed, since clinical studies on the potential of PTP1B inhibition for treating neurological diseases are still required.

蛋白酪氨酸磷酸酶 1B (PTP1B) 是 PTP 家族的典型成员，被认为是几种受体和受体相关酪氨酸激酶的直接负调节剂。这种广泛定位的酶参与了几种疾病的病理生理学。最近，PTP1B 在神经科学领域引起了关注，因为它在脑细胞中的激活会导致精神分裂症样行为缺陷、焦虑样影响、神经退行性变、神经炎症和抑郁症。相反，PTP1B 抑制已被证明可以防止小胶质细胞活化，从而发挥有效的抗炎作用，并且还显示出通过刺激海马胰岛素、瘦素和 BDNF/TrkB 受体来增加认知过程的潜力。虽然，大多数关于靶向 PTP1B 临床疗效的研究都是在肥胖和 2 型糖尿病 (TD2M) 领域开展的。然而，尽管这些代谢改变与神经变性之间存在联系，但尚未进行评估 PTP1B 抑制的神经学优势的临床试验。然而，临床前研究提供了强有力的证据，表明靶向 PTP1B 可以同时达到不同的病理生理机制。因此，应该设计特定的干预措施或试验来调节大脑中的 PTP1B 活性，因为它是减缓或预防老年人神经退行性变以及其他神经系统疾病的有前景的策略。本文未能包括 PTP1B 可能发挥作用的所有神经系统疾病；反而，它侧重于那些与代谢改变和神经退行性过程有关的问题。此外，仅讨论了临床前数据，因为仍需要对 PTP1B 抑制治疗神经系统疾病的潜力进行临床研究。