ASL expression in ALDH1A1+ neurons in the substantia nigra metabolically contributes to neurodegenerative phenotype

Argininosuccinate lyase (ASL) is essential for the NO-dependent regulation of tyrosine hydroxylase (TH) and thus for catecholamine production. Using a conditional mouse model with loss of ASL in catecholamine neurons, we demonstrate that ASL is expressed in dopaminergic neurons in the substantia nigra pars compacta, including the ALDH1A1 + subpopulation that is pivotal for the pathogenesis of Parkinson disease (PD). Neuronal loss of ASL results in catecholamine deficiency, in accumulation and formation of tyrosine aggregates, in elevation of α-synuclein, and phenotypically in motor and cognitive deficits. NO supplementation rescues the formation of aggregates as well as the motor deficiencies. Our data point to a potential metabolic link between accumulations of tyrosine and seeding of pathological aggregates in neurons as initiators for the pathological processes involved in neurodegeneration. Hence, interventions in tyrosine metabolism via regulation of NO levels may be therapeutic beneficial for the treatment of catecholamine-related neurodegenerative disorders

Switched Complex System Analysis for Modeling, Control and diagnosis

International audienceThis paper introduces a methodology of modeling for a class of Non Linear Complex Switched Systems in interaction with their environment. The models have to be adequate either for identification or for diagnosis and control. The effectiveness of this modeling technique is illustrated by experimental results obtained on a greenhouse

An Improved PCA Fault Detection for the Diagnosis

International audienceno abstrac

Neuronal principal component analysis for the diagnosis of a non linear system

International audienceno abstrac

Neuronal principal component analysis for the diagnosis of a non linear system

International audienceno abstrac

An Improved PCA Fault Detection for the Diagnosis

International audienceno abstrac