Neuroprotective and neurogenerative effects of the long-term expression of TNF alpha in the substantia nigra and a new animal model for Parkinson's disease

摘要

Methods for treating a neurodegenerative disease in a mammal, specifically methods for treating Parkinson's disease. The treatment is based on administering an effective amount of a TNF-related molecules and/or TNF down regulating molecules, acting preferably in the substantia nigra. The effects of TNF over the substantia nigra are disclosed. Low concentration of TNF provides a neuroprotective activity and high concentration of TNF provides a neurodegenerative effect on the mammal. The method is based on a treatment with TNF wherein the concentration of TNF in the patients affected by the Parkinson's disease is regulated. In addition, a treatment in which molecules activate a survival signal into neurons via TNFR 2 receptors is provided. A new animal model for Parkinson's disease studies is also provided, wherein the adenovirus vector, the CRE/loxP and transgenic knock-in mice are combined. The transgenic knock in mouse has a transgene comprising a DNA sequence that encodes mTNF in operable linkage with the endogenous engrailed-1 promoter; and a loxP interference cassette downstream of the transgene, wherein the mTNF coding sequence is expressed at low levels in the substantia nigra, and mimics Parkinson's pathological conditions.