The present invention provides methods for treating a neurodegenerative
disease in a subject, preventing a neurodegenerative
disease in a subject, increasing neurons in a region of the brain of a subject, increasing small
ubiquitin-like modifier 1 (SUMO-1) in a region of the brain of a subject, reducing Sentrin-specific
protease 1 (SENP-1) in a region of the brain of a subject, reducing
Serine 129 phosphorylated alpha-
synuclein in a region of the brain of a subject, reducing SENP-1 nuclear translocalization from the
cytosol and / or reducing
protein aggregates in a region of the brain of a subject. The method comprises administering to the subject an effective amount of a pharmaceutical composition comprising a specific SENP-1 inhibitor. The specific SENP-1 inhibitor may be selected from the group consisting of SUMO-2
aldehyde, momordin lc, streptonigrin, hinokiflavone, siRNA of SENP-1, and a combination thereof. Also provided is the pharmaceutical composition.