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.
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