Porphyrias are a group of congenital and acquired diseases caused by an enzymatic impairment in the biosynthesis of heme. Depending on the specific enzyme involved, different types of porphyrias (i.e., chronic vs. acute, cutaneous vs. neurovisceral, hepatic vs. erythropoietic) are described, with different clinical presentations. Acute hepatic porphyrias (AHPs) are characterized by life-threatening acute neuro-visceral crises (acute porphyric attacks, APAs), featuring a wide range of neuropathic (central, peripheral, autonomic) manifestations. APAs are usually unleashed by external “porphyrinogenic” triggers, which are thought to cause an increased metabolic demand for heme. During APAs, the heme precursors -aminolevulinic acid (ALA) and porphobilinogen (PBG) accumulate in the bloodstream and urine. Even though several hypotheses have been developed to explain the protean clinical picture of APAs, the exact mechanism of neuronal damage in AHPs is still a matter of debate. In recent decades, a role has been proposed for oxidative damage caused by ALA, mitochondrial and synaptic ALA toxicity, dysfunction induced by relative heme deficiency on cytochromes and other hemeproteins (i.e., nitric oxide synthases), pyridoxal phosphate functional deficiency, derangements in the metabolic pathways of tryptophan, and other factors. Since the pathway leading to the biosynthesis of heme is inscribed into a complex network of interactions, which also includes some fundamental processes of basal metabolism, a disruption in any of the steps of this pathway is likely to have multiple pathogenic effects. Here, we aim to provide a comprehensive review of the current evidence regarding the mechanisms of neuronal damage in AHPs.
Mechanisms of Neuronal Damage in Acute Hepatic Porphyrias / Ricci, Andrea; Di Pierro, Elena; Marcacci, Matteo; Ventura, Paolo. - In: DIAGNOSTICS. - ISSN 2075-4418. - 11:2205(2021), pp. 1-17. [10.3390/diagnostics11122205]
|Data di pubblicazione:||2021|
|Data di prima pubblicazione:||26-nov-2021|
|Titolo:||Mechanisms of Neuronal Damage in Acute Hepatic Porphyrias|
|Autore/i:||Ricci, Andrea; Di Pierro, Elena; Marcacci, Matteo; Ventura, Paolo|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3390/diagnostics11122205|
|Codice identificativo Scopus:||2-s2.0-85120159734|
|Citazione:||Mechanisms of Neuronal Damage in Acute Hepatic Porphyrias / Ricci, Andrea; Di Pierro, Elena; Marcacci, Matteo; Ventura, Paolo. - In: DIAGNOSTICS. - ISSN 2075-4418. - 11:2205(2021), pp. 1-17. [10.3390/diagnostics11122205]|
|Tipologia||Articolo su rivista|
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