The Role of α-Synuclein and LRRK2 in Tau Phosphorylation
نویسندگان
چکیده
There is now a considerable body of experimental evidence that Parkinson's disease arises through physiological interaction of causative molecules, leading to tau pathology. In this review, we discuss the physiological role of α-synuclein and LRRK2 in the abnormal phosphorylation of tau. In addition, as recent reports have indicated that heat shock proteins- (HSPs-) inducing drugs can help to ameliorate neurodegenerative diseases associated with tau pathology, we also discuss therapeutic strategies for PD focusing on inhibition of α-synuclein- and LRRK2-associated tau phosphorylation by HSPs.
منابع مشابه
Phosphatases of α-synuclein, LRRK2, and tau: important players in the phosphorylation-dependent pathology of Parkinsonism
An important challenge in the field of Parkinson's disease (PD) is to develop disease modifying therapies capable of stalling or even halting disease progression. Coupled to this challenge is the need to identify disease biomarkers, in order to identify pre-symptomatic hallmarks of disease and monitor disease progression. The answer to these challenges lies in the elucidation of the molecular c...
متن کاملLack of exacerbation of neurodegeneration in a double transgenic mouse model of mutant LRRK2 and tau.
LRRK2 (leucine-rich repeat kinase) mutations constitute the most common cause of familial Parkinson's disease (PD). Microtubule-associated protein tau mutations cause a group of neurodegenerative diseases termed tauopathies. Genome-wide association studies show that, after α-synuclein, polymorphisms in the tau gene have the second strongest genetic association with PD. In a proportion of PD pat...
متن کاملHigh LRRK2 Levels Fail to Induce or Exacerbate Neuronal Alpha-Synucleinopathy in Mouse Brain
The G2019S mutation in the multidomain protein leucine-rich repeat kinase 2 (LRRK2) is one of the most frequently identified genetic causes of Parkinson's disease (PD). Clinically, LRRK2(G2019S) carriers with PD and idiopathic PD patients have a very similar disease with brainstem and cortical Lewy pathology (α-synucleinopathy) as histopathological hallmarks. Some patients have Tau pathology. E...
متن کاملEmerging pathways in genetic Parkinson's disease: tangles, Lewy bodies and LRRK2.
The last decade has seen clear links emerge between the genetic determinants and neuropathological hallmarks of parkinsonism and dementia, notably with the discovery of mutations in alpha-synuclein and tau. Following the description of mutations in LRRK2 linked to Parkinson's disease, characterized by variable pathology including either alpha-synuclein or tau deposition, it has been suggested t...
متن کاملRegulation of physiologic actions of LRRK2: focus on autophagy.
BACKGROUND Mutations in LRRK2 are associated with familial and sporadic Parkinson's disease (PD). Subjects with PD caused by LRRK2 mutations show pleiotropic pathology that can involve inclusions containing α-synuclein, tau or neither protein. The mechanisms by which mutations in LRRK2 lead to this pleiotropic pathology remain unknown. OBJECTIVES To investigate mechanisms by which LRRK2 might...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
دوره 2015 شماره
صفحات -
تاریخ انتشار 2015