Alzheimer’s disease (AD) is a progressive neurodegenerative disease and it is the main cause of dementia in elderly. Extracellular deposits of β-amyloid and intraneuronal fibrillary aggregates of tau form the characteristic plaques and tangles, respectively. Autosomal dominant forms of AD, with mutations in the genes encoding β-amyloid precursor protein, presenilin-1 and presenilin-2, have provided insight into the formation of amyloid plaques. Common risk factors for AD are age and the ApoE-genotype (ε4 allele), but many other factors have been implicated in the pathogenesis of AD, including the ubiquitin proteasome system.

Parkinson’s disease (PD) is a neurodegenerative movement disorder, clinically characterized by a resting tremor, by rigidity, hypokinesia and postural instability. The neuropathological hallmarks are intraneuronal Lewy bodies and dystrophic neurites (Lewy neurites), which both contain aggregated proteins, such as α-synuclein, ubiquitinated proteins, parkin and Pael-R (a parkin substrate). The loss of dopaminergic neurons in the substantia nigra pars compacta is the major cause of the clinical movement problems, but it has been shown that there is also more widespread neuropathology in the brains of PD patients. There is strong genetic evidence for the involvement of the UPS in PD, since two of the five genes that are implicated in PD are directly related to the UPS; i.e. parkin, coding for a RING-type E3 ubiquitin ligase and UCH-L1, coding for an enzyme with dual activity, namely a deubiquitination and a ubiquitin ligation activity.