Abstract
Neurodegenerative diseases are linked to a systemic enzyme resistance of toxic aggregated molecules and their pathological consequences. This paper presents a unique phenomenon that Philodina acuticornis, a bdelloid rotifer, is able to catabolize different types of neurotoxic peptide and protein aggregates (such as beta-amyloids /Aβ/, alpha-synuclein, and prion) without suffering any damage. P. acuticornis is capable of using these aggregates as an exclusive energy source (i.e., as ‘food’, identified in the digestive system and body) in a hermetically isolated microdrop environment, increasing their survival. As regards Aβ1–42, five other bdelloid rotifer species were also found to be able to perform this phenomenon. Based on our experiments, the Aβ1–42-treated bdelloid rotifers demonstrate significantly increased survival (e.g. mean lifespan = 51 ± 2.71 days) compared to their untreated controls (e.g. mean lifespan = 14 ± 2.29 days), with similar improvements in a variety of phenotypic characteristics. To our knowledge, no other animal species have so far been reported to have a similar capability. For all other microscopic species tested, including monogonant rotifers and non-rotifers, the treatment with Aβ1–42 aggregates proved to be either toxic or simply ineffective. This paper describes and proves the existence of an unprecedented in vivo catabolic capability of neurotoxic aggregates by bdelloid rotifers, with special focus on P. acuticornis. Our results may provide the basis for a new preclinical perspective on therapeutic research in human neurodegenerative diseases.
Highlights
Neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and prion disease, could be regarded as phenotypes secondary to the progressive functional impairment of proteomes. [29, 52, 53]
The intramolecular regions arranged in β-sheet conformation are highly resistant to enzymatic degradation. [32, 51] The various neurotoxic aggregates, such as those composed of beta-amyloid (Aβ), alphasynuclein (α-Syn), and prion, share common features, with their accumulation and aggregation facilitating neurodegeneration
Misfolded peptide and protein aggregates can be partially digested by several endogenous enzymes, such as insulin-degrading enzyme (IDE) [23], neprilysin (NEP) [16], endothelinconverting enzyme [12], angiotensin-converting enzyme [14], plasmin [47] and matrix metalloproteinases [1]; their presence and function is apparently insufficient in a scenario that leads to neurodegenerative disorders
Summary
Neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and prion disease, could be regarded as phenotypes secondary to the progressive functional impairment of proteomes. [29, 52, 53]. The molecular basis of aging in the brain may be described as an accelerated accumulation accompanied by a decreased clearance and degradation of misfolded proteins [46]. The peptide and protein aggregates in neurodegenerative diseases have several characteristics in common; their different molecular structures and pathomechanism may lead to differences in their toxicity [38]. Misfolded peptide and protein aggregates can be partially digested by several endogenous enzymes, such as insulin-degrading enzyme (IDE) [23], neprilysin (NEP) [16], endothelinconverting enzyme [12], angiotensin-converting enzyme [14], plasmin [47] and matrix metalloproteinases [1]; their presence and function is apparently insufficient in a scenario that leads to neurodegenerative disorders
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